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AIMS: To examine national trends in glucose lowering medicine (GLM) use among older people with diabetes in long-term care facilities (LTCFs) during 2009-2019. METHODS: A repeated cross-sectional study of individuals ≥65 years with diabetes in Australian LTCFs (n = 140,322) was conducted. Annual age-sex standardised prevalence of GLM use and number of defined daily doses (DDDs)/1000 resident-days were estimated. Multivariable Poisson or Negative binomial regression models were used to estimate adjusted rate ratios (aRRs) and 95 % confidence intervals (CIs). RESULTS: Prevalence of GLM use remained steady between 2009 (63.9%, 95 %CI 63.3-64.4) and 2019 (64.3%, 95 %CI 63.9-64.8) (aRR 1.00, 95 %CI 1.00-1.00). The percentage of residents receiving metformin increased from 36.0% (95 %CI 35.3-36.7) to 43.5% (95 %CI 42.9-44.1) (aRR 1.01, 95 %CI 1.01-1.01). Insulin use also increased from 21.5% (95 %CI 21.0-22.0) to 27.0% (95 %CI 26.5-27.5) (aRR 1.02, 95 %CI 1.02-1.02). Dipeptidyl peptidase-4 inhibitor use increased from 1.0% (95 %CI 0.9-1.1) to 21.1% (95 %CI 20.7-21.5) (aRR 1.24, 95 %CI 1.24-1.25), while sulfonylurea use decreased from 34.4% (95 %CI 33.8-35.1) to 19.3% (95 %CI 18.9-19.7) (aRR 0.93, 95 %CI 0.93-0.94). Similar trends were observed in DDDs/1000 resident days. CONCLUSIONS: The increasing use of insulin and ongoing use of sulfonylureas suggests a need to implement evidence-based strategies to optimise diabetes care in LTCFs.
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Background: Diabetes mellitus (DM) is increasing drastically and affecting the individuals globally, especially in the low- and middle-income countries like India. The poor glycaemic control results in micro-vascular and macro-vascular complications, leading to dysfunction of multiple organs. This study aimed to evaluate the association between the risk factors and microalbuminuria levels among patients with type 2 DM on oral hypoglycaemic agents. Materials and Methods: Hundred type 2 DM patients fulfilling the inclusion and exclusion criteria were selected by convenient random sampling. Demographic details, biochemical markers, and anti-diabetic medication details were collected. The findings were analyzed statistically using Chi-square test and one-way analysis of variance (ANOVA) with SPSS software 21.0. Results: Among the different combination therapies, 59% were commonly using metformin and teneligliptin. There was a significant association noted between microalbuminuria and risk factors like age, duration of disease, body mass index (BMI) (25.5 ± 2.9), fasting blood sugar (151 ± 53.2 mg/dL), post prandial blood sugar (227.01 ± 70.9 mg/dL), blood urea (24.42 ± 9.3 mg/dL), and serum creatinine (1.5 ± 0.2 mg/dL) (P < 0.001). One-way ANOVA showed statistical significance between microalbuminuria and the different treatment groups (P < 0.0001). Conclusion: Microalbuminuria was associated with age, duration of diabetes, glycaemic control, and BMI. In contrast, there was no significant difference noted between the genders and microalbuminuria. Microalbuminuria is an early indication of nephropathy in diabetes patients. The early identification of the risk factors is important, and it is always recommended to screen for microalbuminuria in all the diabetic patients for early detection and prevention of diabetic nephropathy and their associated complications.
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PURPOSE: To compare the effect of early vs delayed metformin treatment for glycaemic management among patients with incident diabetes. METHODS: Cohort study using electronic health records of regular patients (1+ visits per year in 3 consecutive years) aged 40+ years with 'incident' diabetes attending Australian general practices (MedicineInsight, 2011-2018). Patients with incident diabetes were defined as those who had a) 12+ months of medical data before the first recording of a diabetes diagnosis AND b) a diagnosis of 'diabetes' recorded at least twice in their electronic medical records or a diagnosis of 'diabetes' recorded only once combined with at least 1 abnormal glycaemic result (i.e., HbA1c ≥6.5%, fasting blood glucose [FBG] ≥7.0 mmol/L, or oral glucose tolerance test ≥11.1mmol/L) in the preceding 3 months. The effect of early (<3 months), timely (3-6 months), or delayed (6-12 months) initiation of metformin treatment vs no metformin treatment within 12 months of diagnosis on HbA1c and FBG levels 3 to 24 months after diagnosis was compared using linear regression and augmented inverse probability weighted models. Patients initially managed with other antidiabetic medications (alone or combined with metformin) were excluded. FINDINGS: Of 18,856 patients with incident diabetes, 38.8% were prescribed metformin within 3 months, 3.9% between 3 and 6 months, and 6.2% between 6 and 12 months after diagnosis. The untreated group had the lowest baseline parameters (mean HbA1c 6.4%; FBG 6.9mmol/L) and maintained steady levels throughout follow-up. Baseline glycaemic parameters for those on early treatment with metformin (<3 months since diagnosis) were the highest among all groups (mean HbA1c 7.6%; FBG 8.8mmol/L), reaching controlled levels at 3 to 6 months (mean HbA1c 6.5%; FBG 6.9mmol/L) with sustained improvement until the end of follow-up (mean HbA1c 6.4%; FBG 6.9mmol/L at 18-24 months). Patients with timely and delayed treatment also improved their glycaemic parameters after initiating treatment (timely treatment: mean HbA1c 7.3% and FBG 8.3mmol/L at 3-6 months; 6.6% and 6.9mmol/L at 6-12 months; delayed treatment: mean HbA1c 7.2% and FBG 8.4mmol/L at 6-12 months; 6.7% and 7.1mmol/L at 12-18 months). Compared to those not managed with metformin, the corresponding average treatment effect for HbA1c at 18-24 months was +0.04% (95%CI -0.05;0.10) for early, +0.24% (95%CI 0.11;0.37) for timely, and +0.29% (95%CI 0.20;0.39) for delayed treatment. IMPLICATIONS: Early metformin therapy (<3 months) for patients recently diagnosed with diabetes consistently improved HbA1c and FBG levels in the first 24 months of diagnosis.
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AIM: To evaluate the long-term safety and efficacy of enavogliflozin 0.3 mg/day added to metformin in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: After 24 weeks of a randomized, double-blind treatment period with enavogliflozin 0.3 mg/day (n = 101) or dapagliflozin 10 mg/day (n = 99) added to metformin, all patients received enavogliflozin 0.3 mg/day plus metformin for an additional 28 weeks during the open-label extension period. RESULTS: Eighty-two patients continued enavogliflozin (maintenance group), and 77 were switched from dapagliflozin to enavogliflozin (switch group). All adverse drug reactions (ADR) were mild in severity. In the maintenance group, ADRs (cystitis and vaginal infection) were reported in two patients (2.44%) during 52 weeks. In the switch group, ADR (hypoglycaemia) was reported in one patient (1.30%) during a 28-week open-label extension period. At week 52, glycated haemoglobin and fasting plasma glucose were significantly lower than at the baseline, by 0.85% and 29.08 mg/dl, respectively, in the maintenance group (p < .0001 for both), and by 0.81% and 32.77 mg/dl, respectively, in the switch group (p < .0001 for both). At week 52, 68.92% of patients from the maintenance group and 64.29% from the switch group achieved glycated haemoglobin <7%. A significant increase in the urine glucose-creatinine ratio was observed at week 52, by 58.81 g/g and 63.77 g/g in the maintenance and switch groups, respectively (p < .0001). CONCLUSIONS: Enavogliflozin added to metformin was tolerated well for up to 52 weeks and provided continual glycaemic control in type 2 diabetes mellitus, along with a significant increase in the urine glucose-creatinine ratio.
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Compostos Benzidrílicos, Glicemia, Diabetes Mellitus Tipo 2, Quimioterapia Combinada, Glucosídeos, Hemoglobinas Glicadas, Hipoglicemiantes, Metformina, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/complicações, Compostos Benzidrílicos/efeitos adversos, Compostos Benzidrílicos/uso terapêutico, Glucosídeos/efeitos adversos, Glucosídeos/uso terapêutico, Glucosídeos/administração & dosagem, Metformina/efeitos adversos, Metformina/uso terapêutico, Metformina/administração & dosagem, Feminino, Pessoa de Meia-Idade, Masculino, Quimioterapia Combinada/efeitos adversos, Método Duplo-Cego, Hipoglicemiantes/efeitos adversos, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Hemoglobinas Glicadas/análise, Hemoglobinas Glicadas/metabolismo, Hemoglobinas Glicadas/efeitos dos fármacos, Glicemia/efeitos dos fármacos, Glicemia/metabolismo, Idoso, Resultado do Tratamento, Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem, Hipoglicemia/induzido quimicamente, Hipoglicemia/epidemiologia, Adulto, BenzofuranosRESUMO
Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.
Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo "cloro" tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.
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Ratos, Modelos Animais, Diabetes Mellitus, Desenvolvimento de Medicamentos, Hipoglicemiantes, AntioxidantesRESUMO
Abstract Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of chloro group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.
Resumo Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo cloro tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.
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AIM: An important characteristic of glucose-lowering therapies (GLTs) is their ability to prevent cardiovascular complications. We aimed to investigate the cardiorenal efficacy and general safety of GLTs. MATERIALS AND METHODS: Multicentre, randomized, clinical trials that included over 100 participants comparing antidiabetic agents with a placebo or a different antidiabetic agent and reporting major adverse cardiovascular events (MACEs), or primarily reporting heart failure, were searched in the PubMed, Embase and Cochrane databases. Data were extracted independently for random-effects network meta-analyses to calculate the hazard ratio estimates. RESULTS: Forty-three trials that compared nine types of GLTs were included in the present analysis. The risk of three-point MACE was reduced in the presence of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and thiazolidinedione therapy compared with the placebo, dipeptidyl peptidase-4 inhibitors, or insulin therapy. GLP-1 RAs were favourable for cardiovascular and renal outcomes. SGLT-2is reduced renal outcomes by ~40%, which was superior to other GLTs. Thiazolidinedione therapy increased the risks of hospitalization for heart failure and had no benefits on mortality. Adverse events leading to drug discontinuation were higher with GLP-1 RAs and thiazolidinediones than placebo. CONCLUSIONS: GLP-1 RAs, SGLT-2is and thiazolidinediones reduced three-point MACE compared with other GLTs. Each drug class had unique advantages and disadvantages.
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Doenças Cardiovasculares, Diabetes Mellitus Tipo 2, Inibidores da Dipeptidil Peptidase IV, Insuficiência Cardíaca, Inibidores do Transportador 2 de Sódio-Glicose, Tiazolidinedionas, Humanos, Hipoglicemiantes/efeitos adversos, Metanálise em Rede, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Diabetes Mellitus Tipo 2/complicações, Ensaios Clínicos Controlados Aleatórios como Assunto, Tiazolidinedionas/efeitos adversos, Inibidores da Dipeptidil Peptidase IV/efeitos adversos, Insuficiência Cardíaca/prevenção & controle, Insuficiência Cardíaca/complicações, Peptídeo 1 Semelhante ao Glucagon/uso terapêutico, Glucose/uso terapêutico, Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas, Doenças Cardiovasculares/epidemiologia, Doenças Cardiovasculares/prevenção & controle, Doenças Cardiovasculares/etiologiaRESUMO
OBJECTIVES: Evaluation of quality of care for patients with diabetes mellitus admitted to hospitals in Spain. METHODS: Cross-sectional study in one day that included 1193 (26.7%) patients with type 2 diabetes or hyperglycaemia out of a total of 4468 patients admitted to the internal medicine departments of 53 hospitals in Spain. We collected demographic data, adequacy of capillary glycaemic monitoring, treatment administered during admission, and recommended therapy at discharge. RESULTS: The median age of the patients was 80 years [74-87], of which 561 (47%) were women, with a Charlson index of 4 points [2-6], and 742 (65%) were fragile. Median blood glucose on admission was 155 mg/dl [119-213]. On the third day, the number of capillary blood glucose levels in target (80-180 mg/dl) at pre-breakfast was 792/1126 (70.3%), pre-lunch 601/1083 (55.4%), pre-dinner 591/1073 (55.0%), and at night 317/529 (59.9%). A total of 35 patients (0.9%) were suffering from hypoglycemia. Treatment during hospitalization was performed with sliding scale insulin in 352 (40.5%) patients, with basal insulin and rapid insulin analogues in 434 (50%), or with diet exclusively in 101 (9.1%). A total of 735 (61.6%) patients had a recent HbA1c value. At discharge, the use of SGLT2i increased significantly (30.1% vs. 21.6%; p < 0.001), as did the use of basal insulin (25.3% vs. 10.1%; p < 0.001). CONCLUSIONS: There is an excessive use of sliding scale insulin as well as insufficient information on HbA1c values and prescription upon discharge of treatments with cardiovascular benefit.
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Diabetes Mellitus Tipo 2, Hiperglicemia, Humanos, Feminino, Idoso de 80 Anos ou mais, Masculino, Hiperglicemia/tratamento farmacológico, Hiperglicemia/induzido quimicamente, Diabetes Mellitus Tipo 2/tratamento farmacológico, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/efeitos adversos, Glicemia, Hemoglobinas Glicadas, Pacientes Internados, Estudos Transversais, Insulina/uso terapêutico, Insulina/efeitos adversos, Hospitais, Insulina Regular HumanaRESUMO
AIMS: To estimate the effectiveness of metformin on glycaemic parameters among participants with incident prediabetes attending Australian general practices. METHODS: This retrospective cohort study used electronic health records of regular participants (3+ visits in two consecutive years) attending 383 Australian general practices (MedicineInsight). Participants with 'incident' prediabetes (newly recorded diagnosis between 2012 and 2017) and their glycaemic parameters (haemoglobin A1c [HbA1c] or fasting blood glucose [FBG]) at 6-, 12-, and 18-24 months post diagnosis (unexposed) or post-management with metformin (treatment) were identified from the database. We estimated the average treatment effect (ATE) of metformin management on glycaemic parameters using both linear regression and augmented inverse probability weighting. RESULTS: Of the 4770 investigated participants with 'incident' prediabetes, 10.2% were managed with metformin. Participants on metformin had higher HbA1c levels at the baseline than those unexposed (mean 45 mmol/mol [6.2%] and 41 mmol/mol [5.9%], respectively), but no differences were observed at 6-12 months (mmol/mol ATE 0.0, 95% CI -0.4; 0.7) or 12-18 months (ATE -0.3, 95% CI -1.2; 0.3). However, participants on metformin had lower mean HbA1c mmol/mol at 18-24 months (ATE -1.1, 95% CI -2.0; 0.1) than those unexposed. Consistent results were observed for FBG (ATE at 6-12 months -0.14 [95% CI -0.25; -0.04], 12-18 months 0.02 [95% CI -0.08; 0.13] and 18-24 months -0.07 [95% CI -0.25; 0.12]). CONCLUSION: The higher HbA1c and FBG baseline levels among participants with 'incident' prediabetes managed with metformin improved after 6-12 months of starting pharmacological management, and the effect persisted for up to 24 months. Management with metformin could prevent further deterioration of glycaemic levels.
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Diabetes Mellitus Tipo 2, Metformina, Estado Pré-Diabético, Humanos, Metformina/uso terapêutico, Estado Pré-Diabético/tratamento farmacológico, Estado Pré-Diabético/epidemiologia, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/epidemiologia, Hemoglobinas Glicadas, Controle Glicêmico, Estudos Retrospectivos, Glicemia, Austrália/epidemiologia, Prontuários Médicos, Atenção Primária à Saúde, Hipoglicemiantes/uso terapêutico, Resultado do TratamentoRESUMO
Background: Rising prevalence and poor outcomes make the twin challenges of diabetes epidemiology. This study evaluates effect of 2-only-daily-meals with exercise (2-OMEX) for its effect on HbA1c, oral hypoglycaemic agents (OHA) usage, body-weight among type-2-diabetes (T2DM) subjects, compared with conventional management. Material and Methods: A quasi-experimental, multicentre study in 2-OMEX arm, and HbA1c by HPLC method. HbA1c and body-weight changes were analyzed by 'Difference in Difference' (DID) method. Meal frequency, exercise, energy intakes were based on recall. The required sample size was 20X2 for 1.1 difference in HbA1c with 95% CL and 80% power. Results: Socio-demographic and risk profile of analysed and omitted subjects were similar. Studied arms were also similar in baseline features. The results in 2-OMEX and conventional arm are: complete records analyzed 201 and 120. Mean (sd) values as follows: observation days 234 and 236, age 52.03(8.84) and 52.45(9.48) years (P=0.6977), diabetes duration 4.6(3.05) and 4.9(2.97) years, BMI 27.28(5.27), 26.90(3.74) (P = 0.1859), baseline HbA1c gm% 7.46(1.52) and 7.55(1.58), end-line proportion of subjects attaining HbA1c ≤6.5gm% was 35.3% and 19.2% (P=0.002), bodyweight loss 2.57% and 1.26%. OHA count 1.6 (1.23) and 2.7(1.06), (P=0.0003). In 2-OMEX arm log-normal HbA1c declined significantly by 0.94 (95%CI: 1.60 to - 0.56, p=0.0333), weight loss difference 0.96 kg, and statistically not significant (P=0.595). Two subjects in 2-OMEX arm showed partial remission. Mean baseline Kcal intakes in 2-OMEX arm, were 1200.4(F) and 1437.3(M) were significantly higher than conventional arm (F) and 1430 (M). Conclusion: The 2-OMEX showed a sizeable and significant reduction in HbA1c and OHA use, in 7-months, with moderate intakes, compared to the conventional arm, possibly attributable to fewer insulin surges. More studies are required for its impact and pathways.
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In modern cardiology, sodium-glucose cotransporter 2 (SGLT2) inhibitors are critical components of heart failure (HF) treatment algorithms and exert their effects primarily by preventing glucose reabsorption and facilitating its urinary excretion. The objective was to systematically review randomized controlled trials (RCTs) assessing the effects of SGLT2 inhibitors, particularly canagliflozin, empagliflozin, dapagliflozin, ertugliflozin, sotagliflozin (dual SGLT inhibitor), and their use in HF. Systematic searches of PubMed/Medline, The Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were performed. There were no restrictions imposed on the date and status of publication; however, there were restrictions on language for the searched studies. A total of 1139 records were identified in the bibliographic searches from both databases and the register of choice for this systematic review. Following duplicate removal, screening for titles and abstracts, and thorough assessment of full-text articles, 12 RCTs met the inclusion criteria. Altogether, 83 878 patients were included in this review. Among the included studies, two RCTs, with six respective reports, investigated canagliflozin, four RCTs with 13 derived reports investigated dapagliflozin, three RCTs with 12 separate reports studied the effects of empagliflozin, one RCT and its three respective reports assessed ertugliflozin's effects, and two RCTs with one added report investigated the dual inhibitor sotagliflozin. Pooled meta-analytic effects of SGLT2 inhibitors were as follows: on atrial fibrillation odds ratio (OR) = 0.83, 95% confidence interval (CI): 0.68-1.01, prediction interval (PI): 0.57-1.19; on HF hospitalization OR = 0.69, 95% CI: 0.60-0.78, PI: 0.60-0.78; on cardiovascular death OR = 0.82, 95% CI: 0.58-1.15, PI: 0.42-1.60; and on major adverse cardiovascular events OR = 0.90, 95% CI: 0.77-1.06, PI: 0.71-1.15. SGLT2 inhibitors significantly improve the quality of life in HF patients. Their beneficial effects on HF, especially in left ventricular dysfunction, have made their use possible irrespective of diabetes mellitus or atrial fibrillation status.
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Fibrilação Atrial, Insuficiência Cardíaca, Inibidores do Transportador 2 de Sódio-Glicose, Humanos, Canagliflozina, Glucose, Insuficiência Cardíaca/tratamento farmacológico, Hipoglicemiantes, Sódio, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
Objective: To evaluate the impact of hepcidin and ferritin in pathogenesis and prognosis of type 2 diabetes mellitus subjects taking only metformin or combined anti-glycaemic agents. METHODS: The observational case-control study was conducted at the Department of Physiology, Baqai Medical University, Karachi, from August 2019 to October 2020, and comprised subjects from both genders who categorised into equal groups as non-diabetic controls, newly-diagnosed type 2 diabetes mellitus patients without any treatment, type 2 diabetes mellitus patients with exposure to metformin only, type 2 diabetes mellitus patients taking oral hypoglycaemic agents along with metformin, type 2 diabetes mellitus patients taking only insulin, and type 2 diabetes mellitus patients taking insulin and oral hypoglycaemic agents. Fasting plasma glucose was determined using glucose oxidase-peroxidase method, glycated haemoglobin by high performance liquid chromatography, high-density lipoprotein and low-density lipoprotein by direct methods, cholesterol by cholesterol oxidase phenol 4-amino antipyrine peroxidase and triglycerides by glycerol phosphate oxidase-phenol 4-amino antipyrine peroxidase method. Serum levels of ferritin, insulin and hepcidin were evaluated using Enzyme-linked immunosorbent assay. Insulin resistance was assessed using homeostasis model assessment for insulin resistance. Data was analysed using SPSS 21. RESULTS: Of the 300 subjects, there were 50(16.66%) in each of the 6 groups. Overall, there were 144(48%) males and 155(51.66%) females. The mean age was significantly lower in the control group 34.72±7.87 compared to all the diabetic groups (p<0.05), and the same was the case with respect to all the parameters (p<0.05) except high-density lipoprotein (p>0.05). Besides, hepcidin level was significantly higher in the control group (p<0.05). Ferritin levels were significantly increased in newly-diagnosed T2DM subjects compared to the controls (p<0.05) while all other groups showed decreased ferritin levels (p<0.05). Hepcidin gave inverse correlation with glycated haemoglobin only in diabetics taking only metformin (r = -0.27, p=0.05). CONCLUSIONS: Anti-diabetes drugs not only addressed type 2 diabetes mellitus, but also reduced levels of ferritin and hepcidin that are found to play a role in diabetes development.
Assuntos
Diabetes Mellitus Tipo 2, Resistência à Insulina, Metformina, Humanos, Feminino, Masculino, Metformina/uso terapêutico, Diabetes Mellitus Tipo 2/tratamento farmacológico, Hepcidinas, Estudos de Casos e Controles, Hemoglobinas Glicadas, Paquistão, Hipoglicemiantes/uso terapêutico, Insulina, PeroxidasesRESUMO
INTRODUCTION: The prevalence of diabetes is increasing in older people. With increasing age, frailty emerges as a new complication leading to disability. Frailty does not only include physical dysfunction but also involves negative impact on cognition and mood. Triad of impairments (TOI) is a new concept that includes physical frailty, dementia and depression to reflect the wider spectrum of frailty. AREAS COVERED: Little is known about effects of hypoglycaemic agents on frailty syndrome. A literature search was performed on studies, which reported effects of hypoglycaemic agents on the component of the TOI. EXPERT OPINION: It appears that most hypoglycaemic agents have some effects on frailty, although the results of clinical studies are inconsistent. Metformin seems to have a consistent and a positive effect on physical frailty. Its effects on cognitive function, however, are inconclusive but tend to be positive. Metformin appeared to improve depressive symptoms. Other agents such as incretins, thiazolidinediones, and sodium glucose transporter-2 inhibitors have some positive effects on cognition and depression. Sulfonylureas, glinides, or insulin have either negative or neutral effects on TOI components. The negative effects of insulin could be partially explained by the negative psychological factors and the frequent episodes of hypoglycemia associated with such therapy.
Assuntos
Diabetes Mellitus Tipo 2, Fragilidade, Metformina, Humanos, Idoso, Hipoglicemiantes/efeitos adversos, Fragilidade/complicações, Fragilidade/tratamento farmacológico, Diabetes Mellitus Tipo 2/complicações, Idoso Fragilizado, Metformina/uso terapêutico, Insulina/uso terapêuticoRESUMO
AIMS: There has been a dramatic increase in hypoglycaemic agent expenditure. We assessed the variability in prescribing costs at the practice level and the relationship between expenditure and the proportion of patients achieving target glycaemic control. METHODS: We utilized national prescribing data from 406 general practices in Wales. This was compared against glycaemic control (percentage of patients achieving a HbA1c level < 59 mmol/mol in the preceding 12 months). Analyses were adjusted for the number of patients with diabetes in each general practice and the Welsh Index of Multiple Deprivation. RESULTS: There was considerable heterogeneity in hypoglycaemic agent spend per patient with diabetes, Median = £289 (IQR 247-343) range £31.1-£1713. Higher total expenditure was not associated with improved glycaemic control B(std) = -0.01 (95%CI -0.01, 0.002) p = 0.13. High-spend practices spent more on SGLT2 inhibitors (16 vs. 9% p < 0.001) and GLP-1 agonists (13 vs. 11% p < 0.001) and less on insulin (34 vs. 42% p < 0.001), biguanides (9 vs. 11% p = 0.001) and sulphonylureas (2 vs. 3% p < 0.001) than low spend practices. There were no differences in the pattern of drug prescribing between high spend practices with better glycaemic control (mean 68% of patients HbA1c <59 mmol/mol) and those with less good metabolic control (mean 58% of patients HbA1c <59 mmol/mol). CONCLUSIONS: Spend on hypoglycaemic agents is highly variable between practices and increased expenditure per patient is not associated with better glycaemic control. Whilst newer, more expensive agents have additional benefits, in individuals where these advantages are more marginal widespread use of these agents has important cost implications.
Assuntos
Diabetes Mellitus Tipo 2, Hipoglicemiantes, Glicemia/metabolismo, Diabetes Mellitus Tipo 2/metabolismo, Hemoglobinas Glicadas/metabolismo, Humanos, Hipoglicemiantes/uso terapêutico, Atenção Primária à Saúde, País de Gales/epidemiologiaRESUMO
OBJECTIVE: To compare clinical outcomes in diabetic patients with heart failure managed by insulin with those managed by non-insulin (oral hypoglycemic agents and/or lifestyle modification) based therapy. METHODS: PubMed and Scopus databases were searched for studies conducted on diabetic patients with heart failure. Studies were to compare outcomes of patients managed by insulin versus non-insulin therapies. RESULTS: 15 studies were included. Compared to those who were managed using non-insulin therapy, insulin-treated patients had increased risk of all-cause mortality (RR 1.46, 95% CI: 1.14, 1.88) and cardiovascular specific mortality (RR 1.62, 95% CI: 1.33, 1.96). Those managed using insulin also had increased risk of hospitalization (RR 1.45, 95% CI: 1.09, 1.93) and readmission (RR 1.49, 95% CI: 1.32, 1.67). There was no additional risk for stroke (RR 1.07, 95% CI: 0.91, 1.27) or myocardial infarction (MI) (RR 1.10, 95% CI: 0.96, 1.27) between the two groups of patients. CONCLUSIONS: Receipt of insulin among diabetic patients with heart failure was associated with an increased risk of mortality, hospitalization and readmission compared to management using oral hypoglycemic agents and/or lifestyle modification. Such patients should be closely monitored for any adverse events.
Assuntos
Diabetes Mellitus, Insuficiência Cardíaca, Infarto do Miocárdio, Diabetes Mellitus/diagnóstico, Diabetes Mellitus/tratamento farmacológico, Diabetes Mellitus/epidemiologia, Insuficiência Cardíaca/diagnóstico, Insuficiência Cardíaca/tratamento farmacológico, Humanos, Hipoglicemiantes/efeitos adversos, Insulina/efeitos adversos, Infarto do Miocárdio/tratamento farmacológicoRESUMO
AIMS: Metformin, rosiglitazone and sulfonylureas enhance either insulin action or secretion and thus have been used extensively as early stage anti-diabetic medication, independently of the aetiology of the disease. When administered to newly diagnosed diabetes patients, these drugs produce variable results. Here, we examined the effects of the three early stage oral hypoglycaemic agents in mice with diabetes induced by multiple low doses of streptozotocin, focusing specifically on the developmental biology of pancreatic islets. METHODS: Streptozotocin-treated diabetic mice expressing a fluorescent reporter specifically in pancreatic islet α-cells were administered the biguanide metformin (100 mg/kg), thiazolidinedione rosiglitazone (10 mg/kg), or sulfonylurea tolbutamide (20 mg/kg) for 10 days. We assessed the impact of the treatment on metabolic status of the animals as well as on the morphology, proliferative potential and transdifferentiation of pancreatic islet cells, using immunofluorescence. RESULTS: The effect of the therapy on the islet cells varied depending on the drug and included enhanced pancreatic islet ß-cell proliferation, in case of metformin and rosiglitazone; de-differentiation of α-cells and ß-cell apoptosis with tolbutamide; increased relative number of ß-cells and bi-hormonal insulin + glucagon + cells with metformin. These effects were accompanied by normalisation of food and fluid intake with only minor effects on glycaemia at the low doses of the agents employed. CONCLUSIONS: Our data suggest that metformin and rosiglitazone attenuate the depletion of the ß-cell pool in the streptozotocin-induced diabetes, whereas tolbutamide exacerbates the ß-cell apoptosis, but is likely to protect ß-cells from chronic hyperglycaemia by directly elevating insulin secretion.
Assuntos
Apoptose/efeitos dos fármacos, Proliferação de Células/efeitos dos fármacos, Secreção de Insulina/efeitos dos fármacos, Ilhotas Pancreáticas, Metformina/farmacologia, Rosiglitazona/farmacologia, Animais, Glicemia/metabolismo, Diferenciação Celular/efeitos dos fármacos, Transdiferenciação Celular/efeitos dos fármacos, Diabetes Mellitus Experimental/tratamento farmacológico, Hipoglicemiantes/farmacologia, Células Secretoras de Insulina/efeitos dos fármacos, Ilhotas Pancreáticas/efeitos dos fármacos, Ilhotas Pancreáticas/metabolismo, CamundongosRESUMO
In France, around 5% of the general population are taking drug treatments for diabetes mellitus (mainly type 2 diabetes mellitus, T2DM). Although the management of T2DM has become more complex, most of these patients are managed by their general practitioner and not a diabetologist for their antidiabetics treatments; this increases the risk of potentially inappropriate prescriptions (PIPs) of hypoglycaemic agents (HAs). Inappropriate prescribing can be assessed by approaches that are implicit (expert judgement based) or explicit (criterion based). In a mixed, multistep process, we first systematically reviewed the published definitions of PIPs for HAs in patients with T2DM. The results will be used to create the first list of explicit definitions. Next, we will complete the definitions identified in the systematic review by conducting a qualitative study with two focus groups of experts in the prescription of HAs. Lastly, a Delphi survey will then be used to build consensus among participants; the results will be validated in consensus meetings. We developed a method for determining explicit definitions of PIPs for HAs in patients with T2DM. The resulting explicit definitions could be easily integrated into computerised decision support tools for the automated detection of PIPs.
RESUMO
AIMS: To use real-world prescription data from Alberta, Canada to: (a) describe the prescribing patterns for initial pharmacotherapy for those with newly diagnosed uncomplicated type 2 diabetes; (b) describe medication-taking behaviours (adherence and persistence) in the first year after initiating pharmacotherapy; and (c) explore healthcare system costs associated with prescribing patterns. METHODS: We employed a retrospective cohort design using linked administrative datasets from 2012 to 2017 to define a cohort of those with uncomplicated incident diabetes. We summarized the initial prescription patterns, adherence and costs (healthcare and pharmaceutical) over the first year after initiation of pharmacotherapy. Using multivariable regression, we determined the association of these outcomes with various sociodemographic characteristics. RESULTS: The majority of individuals for whom metformin was indicated as first-line therapy received a prescription for metformin monotherapy (89%). Older individuals, those with higher baseline A1C and those with no comorbidities, were most likely to be started on non-metformin agents. Adherence with the initially prescribed regimen was suboptimal overall, with nearly half (48%) being non-adherent over the first year. One-third of those who started metformin discontinued it in the first 3 months. Those started on non-metformin agents had roughly twice the healthcare costs, and five to seven times higher medication costs, compared to those started on metformin, in the first year after starting therapy. CONCLUSIONS: With the addition of new classes of medications, healthcare providers who look after those with type 2 diabetes have more pharmaceutical options than ever. Most individuals continue to be prescribed metformin monotherapy. However, adherence is suboptimal, and drops off considerably within the first 3 months.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico, Custos de Medicamentos, Custos de Cuidados de Saúde/tendências, Adesão à Medicação, Metformina/uso terapêutico, Prescrições/estatística & dados numéricos, Adolescente, Adulto, Idoso, Alberta/epidemiologia, Diabetes Mellitus Tipo 2/economia, Diabetes Mellitus Tipo 2/epidemiologia, Feminino, Seguimentos, Humanos, Hipoglicemiantes/uso terapêutico, Masculino, Pessoa de Meia-Idade, Morbidade/tendências, Estudos Retrospectivos, Adulto JovemRESUMO
AIMS: To identify patient-specific factors associated with early metformin treatment modification among type 2 diabetes patients before and after implementation of the updated 2015 NICE (National Institute for Health and Care Excellence) guideline. METHODS: We conducted a population-based cohort study using data from the Clinical Practice Research Datalink GOLD database (2009-2016). Patients ≥ 18 years, newly treated with metformin only, during the period of valid data collection were included. The first prescription defined start of follow-up. Determinants of treatment modification in two cohorts (before and after implementation of the updated guideline) were studied by time-dependent Cox proportional hazards regression. RESULTS: After implementation of the updated guideline, patients were less likely to receive sulphonylureas (62.3% vs 41.3%) or thiazolidediones (4.7% vs 2.2%) and more likely to receive dipeptidyl peptidase-4 inhibitors (15.8% vs 27.1%) or sodium-glucose cotransporter-2 inhibitors (0.8% vs 9.9%). Some determinants influenced general practitioners' prescribing differently after implementation of the updated guideline compared to before, including a high body mass index and heart failure. CONCLUSIONS: Our results indicate that a first step towards tailored prescribing has been made. However, not all determinants that are important to consider when prescribing second-line glucose-lowering agents were of influence on general practitioners' prescribing.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico, Uso de Medicamentos/estatística & dados numéricos, Fidelidade a Diretrizes/estatística & dados numéricos, Hipoglicemiantes, Padrões de Prática Médica/estatística & dados numéricos, Adolescente, Adulto, Idoso, Idoso de 80 Anos ou mais, Estudos de Coortes, Diabetes Mellitus Tipo 2/epidemiologia, Inibidores da Dipeptidil Peptidase IV/uso terapêutico, Substituição de Medicamentos/normas, Substituição de Medicamentos/estatística & dados numéricos, Endocrinologia/história, Endocrinologia/métodos, Endocrinologia/normas, Feminino, História do Século XXI, Humanos, Hipoglicemiantes/classificação, Hipoglicemiantes/normas, Hipoglicemiantes/uso terapêutico, Ciência da Implementação, Masculino, Metformina/uso terapêutico, Pessoa de Meia-Idade, Guias de Prática Clínica como Assunto, Padrões de Prática Médica/normas, Estudos Retrospectivos, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Compostos de Sulfonilureia/uso terapêutico, Adulto JovemRESUMO
AIM: To evaluate the glycaemic efficacy of metformin in people with type 2 diabetes (T2D) and stage 3 chronic kidney disease (CKD3). PARTICIPANTS AND METHODS: This was a retrospective study including 145980 US veterans with T2D and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 who initiated metformin monotherapy between November 1999 and July 2017. Propensity-score-matched cohorts were generated based on baseline variables associated with CKD3 (eGFR 30-59 mL/min/1.73 m2 ) to evaluate the independent association between CKD3 and metformin discontinuation, the addition of a second hypoglycaemic agent, and changes in glycated haemoglobin (HbA1c) from baseline in those with and without CKD3. Associations were examined using the Kaplan-Meier method and multivariable regression models, adjusted for baseline and 12-month average metformin dose. RESULTS: The mean age of the entire cohort was 60.7 years, and 95% of the cohort were men, 21% were African American and 9% had CKD3. In the adjusted analyses, patients with CKD3 had a higher risk of metformin discontinuation or addition of a second hypoglycaemic agent, as compared with patients without CKD (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.19-1.26, and HR 1.26, 95% CI 1.13-1.40, respectively). Among metformin monotherapy users, there were no differences in the average HbA1c reduction from baseline to 12 or 24 months between patients with and without CKD3. CONCLUSIONS: Individuals with CKD3 and T2D were at increased risk of metformin monotherapy failure. However, the HbA1c-lowering efficacy of metformin was similar in patients with and without CKD3, highlighting that metformin is a valuable treatment option for newly treated individuals with T2D and CKD3.
