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1.
Curr Top Med Chem ; 20(1): 37-56, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31884929

RESUMO

BACKGROUND: Type 2 diabetes mellitus is a complex progressive endocrine disease characterized by hyperglycemia and life-threatening complications. It is the most common disorder of pancreatic cell function that causes insulin deficiency. Sulfonylurea is a class of oral hypoglycemic drugs. Over the past half century, these drugs, together with the subsequent non-sulfonylureas (glinides), have been the main oral drugs for insulin secretion. OBJECTIVE: Through in-depth study, the medical profession considers it as an important drug for improving blood sugar control. METHODS: The mechanism, characteristics, efficacy and side effects of sulfonylureas and glinides were reviewed in detail. RESULTS: Sulfonylureas and glinides not only stimulated the release of insulin from pancreatic cells, but also had many extrapanular hypoglycemic effect, such as reducing the clearance rate of insulin in liver, reducing the secretion of glucagon, and enhancing the sensitivity of peripheral tissues to insulin in type 2 diabetes mellitus. CONCLUSION: Sulfonylureas and glinides are effective first-line drugs for the treatment of diabetes mellitus. Although they have the risk of hypoglycemia, weight gain and cardiovascular disease, their clinical practicability and safety can be guaranteed as long as they are reasonably used.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Compostos de Sulfonilureia/farmacologia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Compostos de Sulfonilureia/efeitos adversos , Compostos de Sulfonilureia/uso terapêutico
2.
J Assoc Physicians India ; 67(12): 44-49, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31801331

RESUMO

Background: This study evaluated the adherence and swallowing experience with novel oval-shaped, compact-sized metformin (500 mg/1000 mg)-glimepiride (1mg/2mg) combination, sustained-release tablet (Gluformin G1/Gluformin G2 SR; GM-new-SR) in Indian patients with T2DM, previously treated with conventional metformin-glimepiride combination tablet. Methods: Patients' adherence, swallowing experience, and satisfaction were assessed at baseline and month-3 by Adherence to Refills and Medication Scale (ARMS12; adherent: ARMS12 score=12; nonadherent: ARMS12 score >12) and questionnaire based 5-point Likert scale, respectively. Safety was also assessed. Results: Of 1550 patients enrolled, 1547 (99.8%) completed the study. After 3 months of switching to GM-new-SR tablets, adherence rate increased from 4.38% to 91.1%, with concurrent reduction in mean ARMS-12 score by 6.3±4.36 (p<0.0001). Compared to baseline, all glycemic indices, HbA1c, PPG, and FPG, significantly improved (p<0.0001) in the overall population. Reduction in HbA1c levels was significant only in patients who were adherent to therapy as opposed to nonadherent patients (7.8±1.74 to 7.1±0.85, p<0.0001 vs. 7.7±1.39 to 6.7±0.77, p=0.4276). Most patients attributed ease of swallowing of GM-new-SR tablets to its modified shape (95.5%) and size (94.9%). Most patients (90.4%) were satisfied with the new tablet formulation. Size of the tablet was the most common reason for patients' nonadherence with conventional tablets, which was reported to be less frequent with GM-new-SR tablets (2.5% vs 53.4%). Conclusion: Treatment with GM-new-SR tablets significantly increased adherence and was associated with improvement in glycemic indices, which could be attributed to the compact shape and size of the new tablet formulation.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Glicemia , Deglutição , Quimioterapia Combinada , Hemoglobina A Glicada , Humanos , Adesão à Medicação , Comprimidos
4.
Am J Vet Res ; 80(11): 1001-1006, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31644340

RESUMO

OBJECTIVE: To investigate the ability of a proprietary antagonist of E-type prostanoid receptor (EP) 4, grapiprant, and carprofen to attenuate lameness attributable to urate-induced synovitis in dogs. ANIMALS: 5 purpose-bred hound-cross dogs. PROCEDURES: A blinded, 3-way crossover study was performed. Dogs received each of 3 treatments (L-766, a proprietary antagonist of EP4; 4.0 mg/kg), grapiprant (an antagonist of EP4; 2.0 mg/kg), and carprofen (4.4 mg/kg); dogs received 4 doses of each treatment (14 and 2 hours before and 22 and 46 hours after urate injection). Synovitis was induced by intra-articular injection of sodium urate. Measurements (vertical ground reaction forces and clinical lameness scores) were obtained immediately before (0 hours; baseline) and 6, 12, 24, 36, and 48 hours after sodium urate injection. All data were analyzed with repeated-measures ANOVA. RESULTS: Lameness scores at 6 hours were significantly higher than baseline lameness scores for all treatments. Lameness scores for the grapiprant treatment remained significantly higher at 12 and 24 hours, compared with baseline lameness scores. Lameness scores for the carprofen treatment were significantly lower than lameness scores for the grapiprant treatment at 6, 12, and 24 hours. Analysis of peak vertical force and vertical impulse data revealed a pattern similar to that for lameness scores. Treatment with L-766 resulted in a significantly higher vertical impulse at 48 hours than did treatment with carprofen or grapiprant. CONCLUSIONS AND CLINICAL RELEVANCE: In these dogs, carprofen was the most effective treatment for attenuating lameness induced by injection of sodium urate, and grapiprant was the least effective treatment.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Carbazóis/uso terapêutico , Doenças do Cão/tratamento farmacológico , Coxeadura Animal/tratamento farmacológico , Receptores de Prostaglandina E Subtipo EP4/antagonistas & inibidores , Compostos de Sulfonilureia/uso terapêutico , Sinovite/veterinária , Animais , Carbazóis/farmacologia , Estudos Cross-Over , Cães , Marcha , Injeções Intra-Articulares/veterinária , Coxeadura Animal/induzido quimicamente , Masculino , Método Simples-Cego , Sinovite/induzido quimicamente , Sinovite/tratamento farmacológico , Ácido Úrico
5.
BMC Vet Res ; 15(1): 309, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464629

RESUMO

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are an important tool in the management of canine osteoarthritis, with the most recent introduction into the category being grapiprant, a piprant that selectively targets the EP4 prostaglandin receptor. To date there have been no efficacy studies comparing grapiprant with other NSAIDs. A randomized, two-sequence, assessor-blinded study involving two separate experiments was undertaken to measure the potency and persistence of acute pain control over 24 h resulting from a single oral dose of either firocoxib (Previcox®) or grapiprant (Galliprant®) in an acute arthritis model. RESULTS: Force-plate derived lameness ratios (0, no force recorded on the plate; 1, normal force) for the untreated group remained at 0 for most post-arthritis induction (PAI) assessments in both experiments. Throughout Experiment 1, mean PAI lameness ratios of the firocoxib-treated group remained at or above 0.80. In the grapiprant-treated group, ratios were 0 at 5 and 7 h PAI (7 and 9 h post-treatment), and 0.16 at 10 h PAI (12 h post-treatment). For lameness ratios, relative to the firocoxib group, the control and grapiprant group ratios were significantly lower at each PAI assessment (p ≤ 0.026 and p < 0.001, respectively), except at 1.5 h PAI at which acute pain was still not installed in untreated control dogs. In Experiment 2 the mean lameness ratios for the control group were 0 at 3, 5 and 7 h PAI, and in the grapiprant group at 5, 7 and 10 h PAI (i.e., 19, 21, and 24 h post-treatment). In the firocoxib group the lowest mean lameness ratio of 0.36 occurred at 3 h PAI (i.e. 17 h post-treatment). Except at 1.5 and 3 h PAI (i.e. 15.5 and 17 h post-treatment), due to the needed time for pain to install in the untreated control dogs, the lameness ratio differences between the firocoxib and both the control and grapiprant groups were significant at all assessments (p ≤ 0.033 for both groups). No significant differences were detected between the grapiprant and control groups in either experiment. CONCLUSIONS: Firocoxib treatment prior to induction of arthritis in dogs resulted in a high level of analgesia from the first post-treatment assessment at 1.5 h through 24 h post-treatment. The reduction in lameness provided by firocoxib was consistently superior to that provided by grapiprant, which was not significantly different from untreated controls.


Assuntos
4-Butirolactona/análogos & derivados , Artrite Experimental/veterinária , Doenças do Cão/tratamento farmacológico , Sulfonas/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , 4-Butirolactona/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Cães , Coxeadura Animal , Distribuição Aleatória , Ácido Úrico/toxicidade
6.
Mayo Clin Proc ; 94(8): 1444-1456, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31378227

RESUMO

OBJECTIVE: To compare incident dementia risk among patients who initiated treatment with metformin or sulfonylurea in Veterans Health Affairs (VHA) patients with replication in Kaiser Permanente Washington (KPW) patients to determine whether first-choice antidiabetic medications are associated with reduced risk of dementia. PATIENTS AND METHODS: Cohorts contained 75,187 VHA patients and 10,866 KPW patients, 50 years and older, who initiated monotherapy with metformin or sulfonylurea. Patients were free of dementia diagnoses and any diabetes treatment for 2 years before cohort entry. Variables were extracted from electronic health data from VHA (1999-2015) and KPW (1996-2015), which included diagnosis codes, pharmacy data, laboratory values, and demographic characteristics. Propensity scores and inverse probability of treatment weighting controlled for confounding. RESULTS: Veterans Health Affairs patients were 60.8±6.8 years of age on average, and KPW patients were 63.1±9.5 years of age. In the VHA sample, 72,769 (96.8%) were male; and in the KPW sample, 5480 (50.4%). After adjusting for confounding, metformin initiation was associated with a significantly (P=.02) lower risk of dementia in VHA (hazard ratio, 0.9; 95% CI, 0.9-1.0), with a similar point estimate in KPW (hazard ratio, 0.9; 95% CI, 0.7-1.1). Metformin was not associated with dementia risk in patients 75 years and older. CONCLUSION: Existing epidemiological studies of metformin and incident dementia have been inconsistent. Using a similar study design in 2 patient populations that differed in clinical and demographic characteristics, our results provide robust evidence that metformin use is associated with a modestly lower risk of incident dementia.


Assuntos
Demência/induzido quimicamente , Demência/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/efeitos adversos , Compostos de Sulfonilureia/efeitos adversos , Fatores Etários , Idoso , Bases de Dados Factuais , Demência/fisiopatologia , Diabetes Mellitus Tipo 2/diagnóstico , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Hospitais de Veteranos , Humanos , Incidência , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Compostos de Sulfonilureia/uso terapêutico , Estados Unidos
7.
Diabetes Res Clin Pract ; 155: 107796, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31326458

RESUMO

AIM: The aim of this study was to analyze the efficacy, insulin sensitivity and safety in the event of administering sulfonylurea-based drugs and metformin in combination with basal insulin. METHODS: A randomized, open-label, parallel, 16-week trial was conducted across four study centers. The 97 type 2 diabetic patients were selected and randomized into two groups, the insulin glargine plus fixed-dose combination glimepiride 1 mg and metformin 500 mg twice daily group (the G/M group) and the insulin glargine plus glimepiride 4 mg once daily group (the G group). The primary endpoint evaluated was change in HbA1c. The secondary endpoints evaluated were changes in fasting blood glucose (FPG), 2-h post prandial glucose (PPG 2 h), insulin, and C-peptide levels. RESULTS: The G/M group was found to have experienced a significantly greater decrease in HbA1c, as well as PPG 2 h compared to the G group. While no significant intergroup difference was found regarding FPG in the ITT, the G/M group in the PP set experienced a significantly greater decrease in FPG. CONCLUSION: Comparison of combined therapy consisting of either the G/M group or the G group indicated that both forms of therapy are relatively safe but that the former more effectively decreases blood glucose levels.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Insulina/uso terapêutico , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Feminino , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Segurança
8.
Clin Drug Investig ; 39(6): 521-531, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31041606

RESUMO

BACKGROUND AND OBJECTIVE: When metformin is insufficient for patients with type 2 diabetes mellitus (T2DM), the optimal adjunctive therapy is unclear. This meta-analysis was to compare the efficacy and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors with sulfonylureas (SUs) as second-line therapy in patients with T2DM inadequately controlled on metformin. METHODS: We systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for randomized controlled trials comparing SGLT2 inhibitors with SUs as add-on to metformin. Our primary endpoints were glycemic control, hypoglycemia, and change in weight. We assessed pooled data using a random-effects model. RESULTS: Five trials involving 4300 participants were included in our meta-analysis. Compared with SUs, SGLT2 inhibitors led to no significant reduction in changes in HbA1c (mean difference [MD] - 0.06; 95% confidence interval [CI] [- 0.12, 0.08]), but less hypoglycemia as add-on to metformin (odds ratio [OR] 0.12; 95% CI [0.07, 0.21]). SGLT2 inhibitors led to a reduction in weight by about 3.5 kg; however, SUs caused a gain in weight by about 1 kg (MD - 4.39; 95% CI [- 4.64, - 4.14]). SGLT2 inhibitors also showed a reduction in blood pressure, but increased the incidence of genital tract infections compared with SUs. Interestingly, subgroup analysis by duration of interventions showed that reduction of HbA1c from baseline was similar between the two groups at 12-52 weeks, but SGLT2 inhibitors led to a greater reduction in HbA1c at 104-208 weeks. CONCLUSIONS: Despite similar glycemic efficacy in a relatively short term, SGLT2 inhibitors are more effective in the longer term than SUs as add-on to metformin. In addition, SGLT2 inhibitors produce less hypoglycemic events and lead to greater reductions in weight and blood pressure compared with SUs.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Glicemia , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Metformina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Diabetes Res Clin Pract ; 152: 103-110, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31108137

RESUMO

AIMS: Several insulin secretagogues are widely used to treat diabetes; however, few outcome-based comparative studies have clarified which one of these should be used when indicated. We investigated mortality and cardiovascular event risk associated with optimal forms of insulin secretagogues. METHODS: In this cohort study using real-world data from the diabetes database of Taiwan's National Health Insurance program, patients with diabetes were enrolled if their initial treatment was glimepiride, gliclazide, glipizide, glyburide, or repaglinide from 1999 to 2013. Each group was propensity score-matched to the glimepiride group before comparison. Primary outcomes were all-cause mortality and the combined cardiovascular event risk of acute myocardial infarction and ischemic stroke. Hazard ratios were calculated by Cox proportional hazard regression models. RESULTS: There were 66,790, 97,426, 38,806, 92,970, and 11,468 participants in the glimepiride, gliclazide, glipizide, glyburide, and repaglinide groups, respectively. The median follow-up time was 8 years. Glimepiride was associated with the best clinical outcome, showing the lowest mortality and lowest cardiovascular event risk of the five insulin secretagogues. Using patients on glimepiride as the reference group, the adjusted hazard ratios of all-cause mortality and cardiovascular event risk were 1.52 (p < 0.001) and 1.22 (p = 0.005) for gliclazide, 1.42 (p < 0.001) and 1.19 (p = 0.073) for glipizide, 1.43 (p < 0.001) and 1.32 (p < 0.001) for glyburide, and 1.88 (p < 0.001) and 1.69 (p = 0.001) for repaglinide. CONCLUSIONS: For patients with diabetes taking an insulin secretagogue, glimepiride was associated with the best clinical outcome, showing the lowest mortality and cardiovascular event risk.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Hipoglicemiantes/uso terapêutico , Secreção de Insulina/efeitos dos fármacos , Secretagogos/uso terapêutico , Idoso , Carbamatos/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/induzido quimicamente , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/mortalidade , Feminino , Seguimentos , Gliclazida/uso terapêutico , Glipizida/uso terapêutico , Glibureto/uso terapêutico , Humanos , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Mortalidade , Piperidinas/uso terapêutico , Secretagogos/farmacologia , Compostos de Sulfonilureia/uso terapêutico , Taiwan/epidemiologia
11.
J Clin Pharm Ther ; 44(5): 720-725, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31094010

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Teneligliptin is a DPP-4 inhibitor used for the treatment of type 2 diabetes mellitus, commonly prescribed in combination with glimepiride. Teneligliptin is metabolized by CYP3A4, and glimepiride might be partly metabolized by CYP3A4. The aim of the study was to investigate the possible effect of glimepiride on the pharmacokinetics of teneligliptin in healthy subjects. METHODS: A repeated dose, open-label, fixed-sequence study was conducted in 26 healthy subjects. All participants were administered 20 mg teneligliptin daily for 6 days. On day 7, 4 mg glimepiride was administered together with 20 mg teneligliptin. Plasma teneligliptin concentrations were measured at a steady state, and its pharmacokinetic characteristics were compared without and with glimepiride. RESULTS AND DISCUSSION: No statistically significant difference was found in the effect of glimepiride on teneligliptin pharmacokinetics. The steady-state Cmax,ss values of teneligliptin without and with glimepiride were 207.01 ng/mL and 202.15 ng/mL, respectively. Its AUCτ values at steady-state without and with glimepiride were 1527.8 ng · h/mL and 1578.6 ng · h/mL, respectively. The point estimation of geometric mean ratios (GMR) and the 90% confidence interval for both Cmax,ss and AUCτ were within the equivalence range of 0.8-1.25. The results of the present study revealed that glimepiride did not cause pharmacokinetic interaction with teneligliptin in humans. WHAT IS NEW AND CONCLUSION: Glimepiride did not affect the pharmacokinetic characteristics of teneligliptin in healthy subjects.


Assuntos
Interações de Medicamentos/fisiologia , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Pirazóis/farmacocinética , Compostos de Sulfonilureia/efeitos adversos , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinas/farmacocinética , Adulto , Diabetes Mellitus Tipo 2/metabolismo , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Adulto Jovem
12.
J Pak Med Assoc ; 69(4): 555-563, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31000862

RESUMO

Sodium-glucose co-transporter type 2 inhibitors (SGLT 2- i)are increasingly being used in the management of type 2 diabetes mellitus (T2DM). With the novel insulinindependent glycosuric action, these agents help to attain glycaemic goals by lowering HbA1c and fasting blood glucose. In addition, these agents improve metabolic control in diabetes and ameliorate comorbidities like obesity and hyper tension. Beneficial effec ts on cardiovascular outcomes have been a key attraction for physicians. These agents are used alone or in combination with oral antidiabetic agents and insulin to attain glycaemic and metabolic targets. A major disadvantagewith these agents is the increased risk for genital andurinary infections. When used in appropriate settings, there is no additional increased risk of hypoglycaemia or volume depletion with these agents. Available evidence suggests good efficacy and safety of these agents in diabetes management. The easy and convenient oncedaily dosing should be customized according to patient needs and glycaemic profiles.


Assuntos
Grupo com Ancestrais do Continente Asiático , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Ásia Sudeste , Ásia Ocidental , Pressão Sanguínea , Peso Corporal , Colesterol , HDL-Colesterol , LDL-Colesterol , Creatinina , Quimioterapia Combinada , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , Hepatopatia Gordurosa não Alcoólica , Paquistão , Albumina Sérica , Compostos de Sulfonilureia/uso terapêutico
13.
Cochrane Database Syst Rev ; 4: CD012368, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30998259

RESUMO

BACKGROUND: The number of people with type 2 diabetes mellitus (T2DM) is increasing worldwide. The combination of metformin and sulphonylurea (M+S) is a widely used treatment. Whether M+S shows better or worse effects in comparison with other antidiabetic medications for people with T2DM is still controversial. OBJECTIVES: To assess the effects of metformin and sulphonylurea (second- or third-generation) combination therapy for adults with type 2 diabetes mellitus. SEARCH METHODS: We updated the search of a recent systematic review from the Agency for Healthcare Research and Quality (AHRQ). The updated search included CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO ICTRP. The date of the last search was March 2018. We searched manufacturers' websites and reference lists of included trials, systematic reviews, meta-analyses and health technology assessment reports. We asked investigators of the included trials for information about additional trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) randomising participants 18 years old or more with T2DM to M+S compared with metformin plus another glucose-lowering intervention or metformin monotherapy with a treatment duration of 52 weeks or more. DATA COLLECTION AND ANALYSIS: Two review authors read all abstracts and full-text articles and records, assessed risk of bias and extracted outcome data independently. We used a random-effects model to perform meta-analysis, and calculated risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the certainty of the evidence using the GRADE instrument. MAIN RESULTS: We included 32 RCTs randomising 28,746 people. Treatment duration ranged between one to four years. We judged none of these trials as low risk of bias for all 'Risk of bias' domains. Most important events per person were all-cause and cardiovascular mortality, serious adverse events (SAE), non-fatal stroke (NFS), non-fatal myocardial infarction (MI) and microvascular complications. Most important comparisons were as follows:Five trials compared M+S (N = 1194) with metformin plus a glucagon-like peptide 1 analogue (N = 1675): all-cause mortality was 11/1057 (1%) versus 11/1537 (0.7%), risk ratio (RR) 1.15 (95% confidence interval (CI) 0.49 to 2.67); 3 trials; 2594 participants; low-certainty evidence; cardiovascular mortality 1/307 (0.3%) versus 1/302 (0.3%), low-certainty evidence; serious adverse events (SAE) 128/1057 (12.1%) versus 194/1537 (12.6%), RR 0.90 (95% CI 0.73 to 1.11); 3 trials; 2594 participants; very low-certainty evidence; non-fatal myocardial infarction (MI) 2/549 (0.4%) versus 6/1026 (0.6%), RR 0.57 (95% CI 0.12 to 2.82); 2 trials; 1575 participants; very low-certainty evidence.Nine trials compared M+S (N = 5414) with metformin plus a dipeptidyl-peptidase 4 inhibitor (N = 6346): all-cause mortality was 33/5387 (0.6%) versus 26/6307 (0.4%), RR 1.32 (95% CI 0.76 to 2.28); 9 trials; 11,694 participants; low-certainty evidence; cardiovascular mortality 11/2989 (0.4%) versus 9/3885 (0.2%), RR 1.54 (95% CI 0.63 to 3.79); 6 trials; 6874 participants; low-certainty evidence; SAE 735/5387 (13.6%) versus 779/6307 (12.4%), RR 1.07 (95% CI 0.97 to 1.18); 9 trials; 11,694 participants; very low-certainty evidence; NFS 14/2098 (0.7%) versus 8/2995 (0.3%), RR 2.21 (95% CI 0.74 to 6.58); 4 trials; 5093 participants; very low-certainty evidence; non-fatal MI 15/2989 (0.5%) versus 13/3885 (0.3%), RR 1.45 (95% CI 0.69 to 3.07); 6 trials; 6874 participants; very low-certainty evidence; one trial in 64 participants reported no microvascular complications were observed (very low-certainty evidence).Eleven trials compared M+S (N = 3626) with metformin plus a thiazolidinedione (N = 3685): all-cause mortality was 123/3300 (3.7%) versus 114/3354 (3.4%), RR 1.09 (95% CI 0.85 to 1.40); 6 trials; 6654 participants; low-certainty evidence; cardiovascular mortality 37/2946 (1.3%) versus 41/2994 (1.4%), RR 0.78 (95% CI 0.36 to 1.67); 4 trials; 5940 participants; low-certainty evidence; SAE 666/3300 (20.2%) versus 671/3354 (20%), RR 1.01 (95% CI 0.93 to 1.11); 6 trials; 6654 participants; very low-certainty evidence; NFS 20/1540 (1.3%) versus 16/1583 (1%), RR 1.29 (95% CI 0.67 to 2.47); P = 0.45; 2 trials; 3123 participants; very low-certainty evidence; non-fatal MI 25/1841 (1.4%) versus 21/1877 (1.1%), RR 1.21 (95% CI 0.68 to 2.14); P = 0.51; 3 trials; 3718 participants; very low-certainty evidence; three trials (3123 participants) reported no microvascular complications (very low-certainty evidence).Three trials compared M+S (N = 462) with metformin plus a glinide (N = 476): one person died in each intervention group (3 trials; 874 participants; low-certainty evidence); no cardiovascular mortality (2 trials; 446 participants; low-certainty evidence); SAE 34/424 (8%) versus 27/450 (6%), RR 1.68 (95% CI 0.54 to 5.21); P = 0.37; 3 trials; 874 participants; low-certainty evidence; no NFS (1 trial; 233 participants; very low-certainty evidence); non-fatal MI 2/215 (0.9%) participants in the M+S group; 2 trials; 446 participants; low-certainty evidence; no microvascular complications (1 trial; 233 participants; low-certainty evidence).Four trials compared M+S (N = 2109) with metformin plus a sodium-glucose co-transporter 2 inhibitor (N = 3032): all-cause mortality was 13/2107 (0.6%) versus 19/3027 (0.6%), RR 0.96 (95% CI 0.44 to 2.09); 4 trials; 5134 participants; very low-certainty evidence; cardiovascular mortality 4/1327 (0.3%) versus 6/2262 (0.3%), RR 1.22 (95% CI 0.33 to 4.41); 3 trials; 3589 participants; very low-certainty evidence; SAE 315/2107 (15.5%) versus 375/3027 (12.4%), RR 1.02 (95% CI 0.76 to 1.37); 4 trials; 5134 participants; very low-certainty evidence; NFS 3/919 (0.3%) versus 7/1856 (0.4%), RR 0.87 (95% CI 0.22 to 3.34); 2 trials; 2775 participants; very low-certainty evidence; non-fatal MI 7/890 (0.8%) versus 8/1374 (0.6%), RR 1.43 (95% CI 0.49 to 4.18; 2 trials); 2264 participants; very low-certainty evidence; amputation of lower extremity 1/437 (0.2%) versus 1/888 (0.1%); very low-certainty evidence.Trials reported more hypoglycaemic episodes with M+S combination compared to all other metformin-antidiabetic agent combinations. Results for M+S versus metformin monotherapy were inconclusive. There were no RCTs comparing M+S with metformin plus insulin. We identified nine ongoing trials and two trials are awaiting assessment. Together these trials will include approximately 16,631 participants. AUTHORS' CONCLUSIONS: There is inconclusive evidence whether M+S combination therapy compared with metformin plus another glucose-lowering intervention results in benefit or harm for most patient-important outcomes (mortality, SAEs, macrovascular and microvascular complications) with the exception of hypoglycaemia (more harm for M+S combination). No RCT reported on health-related quality of life.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Quimioterapia Combinada , Humanos , Hipoglicemia/induzido quimicamente , Resultado do Tratamento
14.
Acta Diabetol ; 56(8): 889-897, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30963308

RESUMO

AIMS: The impact of introducing new classes of glucose-lowering medication (GLM) on diabetes management remains unclear, especially outside North America and Western Europe. Therefore, we aimed to analyse trends in glycaemic control and the usage of new and old GLMs in people with type 2 diabetes from 2006 to 2015. METHODS: Summary data from clinical services from nine countries outside North America and Western Europe were collected and pooled for statistical analysis. Each site summarized individual-level data from out-patient medical records for 2006 and 2015. Data included: demographics; HbA1c and fasting plasma glucose levels; and the proportions of patients taking GLM as monotherapy, combination therapy and/or insulin. RESULTS: Between 2006 and 2015, glycaemic control remained stable, although body mass index and duration of diabetes increased in most sites. The proportion of people on GLM increased, and the therapeutic regimens became more complex. There were increases in the use of insulin and triple therapy in most sites, while monotherapy, particularly in relation to sulphonylureas, decreased. Despite the introduction of new GLMs, such as DPP-4 inhibitors, insulin use increased over time. CONCLUSIONS: There was no clear evidence that the use of new classes of GLMs was associated with improvements in glycaemic control or reduced the reliance on insulin. These findings were consistent across a range of economic and geographic settings.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Insulina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Gerenciamento Clínico , Europa (Continente) , Humanos , Insulina/administração & dosagem , América do Norte , Compostos de Sulfonilureia/administração & dosagem
15.
Diabetes Res Clin Pract ; 151: 65-73, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30954510

RESUMO

AIMS: To directly compare the effectiveness and safety between two distinct sodium-glucose co-transporter 2 (SGLT2) inhibitors, empagliflozin and dapagliflozin, as part of a quadruple oral antidiabetic agents (OADs) in patients with inadequately controlled type 2 diabetes (T2D). METHODS: This study was an open-labeled, prospective, 52-week study conducted in T2D patients with glycated hemoglobin (HbA1c) ranging 7.5-12.0% with metformin, glimepiride and dipeptidyl peptidase-4 inhibitors. Patients were divided into either empagliflozin (25 mg/day) or dapagliflozin (10 mg/day). The outcome measures included changes in HbA1c, fasting plasma glucose (FPG), and cardiometabolic variables and the safety profiles. RESULTS: In total, 350 patients were enrolled with empagliflozin (n = 176) and dapagliflozin (n = 174), respectively. After 52 weeks, both groups showed significant reductions in HbA1c and FPG, but the reduction was greater in the empagliflozin group (P < 0.001). Both groups showed significantly decreased blood pressure and body weight and high-density lipoprotein cholesterol levels were increased in the empagliflozin (between groups, P = 0.035). Both groups showed similar safety profiles. CONCLUSIONS: Our study demonstrated that SGLT2 inhibitors can be effectively used as a fourth OAD in T2D patients who are treated with three other OADs. More specifically, empagliflozin was more effective in reducing HbA1c and improving other cardiometabolic parameters than dapagliflozin. Clinical Trial Number NCT03748810 (ClinicalTrials.gov).


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Quimioterapia Combinada/métodos , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos Benzidrílicos/farmacologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Método Duplo-Cego , Feminino , Glucosídeos/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Masculino , Metformina/farmacologia , Pessoa de Meia-Idade , Estudos Prospectivos , Compostos de Sulfonilureia/farmacologia , Adulto Jovem
16.
Diabetes Res Clin Pract ; 152: 177-182, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30946851

RESUMO

AIMS: To describe the attitude of type 2 diabetes patients toward Ramadan fasting. A Secondary purpose was to describe rates of hypoglycemia during Ramadan according to type of treatment. METHODS: A prospective, non-randomized study for 2 years. Participants with type 2 diabetes attending Dammam Diabetes Center, Saudi Arabia were stratified for fasting according to ADA recommendations. Results are presented using mean, standard deviation and percentages. RESULTS: Total of 360 participants with type 2 diabetes. Mean ±â€¯SD glycosylated hemoglobin was 8.9 ±â€¯2.1. More than 80% of individuals were in the ADA higher risk group however, they all fasted Ramadan. The mean non-fasting days was 2.6 days and overall rate of hypoglycaemia was 24.7%. Both parameters were directly proportionate to the risk stratification level (P-value <0.05). Despite hypoglycaemia, 29.3% continued fasting. Hypoglycemia was highest in patients treated with insulin (P-value <0.05) followed by those treated with oral agents including sulphonylurea as compared to oral agents excluding sulfonylurea (P-value = 0.002). Those who experienced hypoglycemia prior to Ramadan had the highest rate of hypoglycemia during Ramadan (53.3%) (P-value = 0.0065). CONCLUSIONS: Despite medical advice, the vast majority of type 2 diabetes participants categorized as high risk, fasted Ramadan. Approximately one quarter of people with type 2 diabetes in our cohort experience hypoglycaemia and this was directly related to their fasting risk level. A sizeable proportion continued the fast despite hypoglycemic. Insulin therapy with or without oral agents and previous episodes of hypoglycemia before Ramadan predicted hypoglycemia risk during Ramadan. HbA1c and weight showed some clinical improvements post Ramadan fasting. This is a single center study of mostly high risk fasting patients and hence, these results should not be generalized.


Assuntos
Atitude Frente a Saúde , Diabetes Mellitus Tipo 2 , Jejum , Conhecimentos, Atitudes e Prática em Saúde , Islamismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/psicologia , Jejum/efeitos adversos , Jejum/psicologia , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Islamismo/psicologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Arábia Saudita/epidemiologia , Compostos de Sulfonilureia/uso terapêutico , Inquéritos e Questionários , Adulto Jovem
17.
Clin Respir J ; 13(5): 299-305, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30815978

RESUMO

BACKGROUND AND OBJECTIVES: There are limited data about the risk of asthma in people with diabetes. We examined the incidence of asthma in subjects with type 2 diabetes (T2DM) compared to controls, and the association with metformin, sulphonylureas and insulin therapy. MATERIALS AND METHODS: We conducted a retrospective cohort study using a representative UK primary care database (N = 894 646 adults). We used 1:1 propensity score matching (age, gender, socio-economic deprivation, body mass index and smoking status) to match 29 217 pairs of T2DM cases and controls. We used Cox proportional hazard regression to compare the incidence of asthma in both groups over 8 years of follow-up. In those with T2DM, we used Cox proportional hazard regression to assess for any impact of antidiabetic medications on asthma incidence. RESULTS: Individuals with T2DM were less likely to develop asthma than matched controls (hazard ratio [HR] 0.85, 95% CI 0.77-0.93). Insulin increased the risk of incident asthma (HR 1.25, 95% CI 1.01-1.56), whilst metformin and sulphonylureas were associated with reduced risk (HR 0.80, 95% CI 0.69-0.93 and HR 0.76, 95% CI 0.60-0.97, respectively). There was no association with diabetes duration, complications or glycaemic control. CONCLUSIONS: T2DM may have a protective effect against asthma development. Insulin use was associated with an increased risk of asthma, while metformin and sulphonylureas reduced the risk in those with T2DM.


Assuntos
Asma/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Idoso , Estudos de Casos e Controles , Inglaterra/epidemiologia , Humanos , Incidência , Insulina/uso terapêutico , Metformina/uso terapêutico , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Risco , Compostos de Sulfonilureia/uso terapêutico
18.
Medicine (Baltimore) ; 98(8): e14370, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813137

RESUMO

The purpose of this study was to describe the prescription pattern of initial treatment for type 2 diabetes (T2DM) in Beijing from 2011 to 2015.We selected 790,339 newly diagnosed outpatients with T2DM from the Beijing Medical Claim Data for Employees database between January 2011 and December 2015. The percentages of different treatments and agents were calculated from the patients' 1st prescriptions. Subgroup analyses were conducted for primary, secondary, and tertiary hospital settings.The initial treatments given to 57.7%, 30.7%, and 11.7% of patients were oral hypoglycemic agent (OHA) monotherapy, OHA polytherapy, and insulin, respectively. Alpha-glucosidase inhibitors (AGIs) (43.0%) were the most commonly used agents for monotherapy, followed by metformin (35.5%) and sulfonylureas (14.9%). AGIs were most commonly used in primary hospitals (52.0%), while metformin was prescribed most often in secondary (37.6%) and tertiary (41.8%) hospitals. From 2011 to 2015, there were increases in the use of AGIs (40.1-41.1%, P < .001) and metformin (34.0-40.4%, P < .001), but a decrease in the use of sulfonylureas (18.1-12.8%, P < .001). Similar trends were seen in the different hospital settings. Metformin plus an AGI, a sulfonylurea plus an AGI, and metformin plus a sulfonylurea were the most common OHA polytherapy combinations. The use of metformin plus an AGI increased from 13.8% in 2011 to 19.7% in 2015 (P < .001), while the use of a sulfonylurea plus an AGI, and metformin plus a sulfonylurea, did not change significantly.Half of newly diagnosed patients with T2DM received an initial treatment of OHA monotherapy. Although the use of metformin increased from 2011 to 2015, both AGIs and metformin were the most commonly prescribed agents. The patterns differed from those of most other countries and identification of the underlying reasons will require further investigation.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Padrões de Prática Médica , Adulto , Idoso , Pequim , Prescrições de Medicamentos/estatística & dados numéricos , Quimioterapia Combinada , Feminino , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Humanos , Insulina/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Compostos de Sulfonilureia/uso terapêutico
19.
Stroke ; 50(4): 995-998, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30879436

RESUMO

Background and Purpose- Sulfonylurea medications have been linked to reduced brain edema and improved outcome following ischemic stroke, but their effects on primary intracerebral hemorrhage (pICH) have not been thoroughly explored. Increasing ICH volume and perihematomal edema (PHE) volume are predictors of poor outcome in pICH. We investigated whether preexisting sulfonylurea use influenced ICH volume, PHE volume, and discharge disposition in patients with type 2 diabetes mellitus presenting with pICH. Methods- We performed a retrospective chart review of all diabetic patients presenting with pICH to 2 tertiary academic centers from 2006 to 2016. All patients with diabetes mellitus, pICH, admission computed tomography scan, and sulfonylurea use on admission were included in our study. For each case, 2-matched controls (admission date, age, hematoma location [deep versus lobar], use of antiplatelet, or anticoagulant) with diabetes mellitus and pICH were consecutively selected. ICH and PHE volumes were measured via region of interest analysis on admission computed tomography. To mitigate the influence of ICH volume on PHE, the PHE/ICH surface area ratio was calculated. Hospital discharge disposition was determined via chart abstraction. We used the Wilcoxon rank-sum test and Fisher exact test to compare cases and controls. Results- Of 317 patients screened, 21 sulfonylurea cases and 42-matched controls met criteria for study inclusion. Sulfonylurea cases had significantly lower admission ICH volumes (median, 4 mL; interquartile range [IQR], 2-30 versus median, 25 mL; IQR, 6-60; P=0.011), PHE volumes (median, 4 mL; IQR, 0.9-24 versus median, 17; IQR, 6-37; P=0.0095), and PHE/ICH surface area ratios (median, 0.28; IQR, 0.1-0.4 versus median, 0.43; IQR, 0.3-0.6; P=0.013) as compared with controls. Sulfonylureas were associated with improved discharge disposition ( P=0.0062). Conclusions- In patients with diabetes mellitus and pICH, sulfonylurea use predicted lower ICH and PHE volumes, lower relative PHE, and improved discharge disposition. Given the paucity of treatment options for pICH, further study of sulfonylureas is warranted.


Assuntos
Edema Encefálico/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Compostos de Sulfonilureia/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Edema Encefálico/complicações , Estudos de Casos e Controles , Hemorragia Cerebral/complicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
20.
BMC Cardiovasc Disord ; 19(1): 60, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30876392

RESUMO

BACKGROUND: Cardiovascular (CV) disease (CVD) is a well-recognized complication of type 2 diabetes mellitus (T2DM) and there is a clinical need for glucose-lowering therapies that do not further increase CV risk in this population. Although sulfonylureas (SUs) may be used as second-line therapy for patients requiring additional therapy after first-line metformin to improve glycemic control, their long-term effects on CV outcomes remain uncertain, and a wide range of alternative agents exist including dipeptidyl peptidase-4 (DPP-4) inhibitors. METHODS: Literature searches in PubMed (2013-2018) were conducted with terms for DPP-4 inhibitors combined with CV terms, with preference given to cardiovascular outcomes trials (CVOTs). Reference lists from retrieved articles and diabetes guidelines were also considered. RESULTS: This narrative review discusses current evidence for the CV safety of these agents, describes the long-term CV effects of DPP-4 inhibitors, including effects on CV events, mortality, the risk for heart failure hospitalization, and highlights the need for further research into the CV effects of SU therapy. Although SUs remain a treatment option for T2DM, the long-term effects of these agents on CV outcomes are unclear, and further long-term studies are required. For DPP-4 inhibitors, uncertainties have been raised about their long-term effect on hospitalization for heart failure in light of the results of SAVOR-TIMI 53, although the findings of other DPP-4 inhibitor CVOTs in T2DM and data analyses have suggested these agents do not increase the occurrence of adverse CV outcomes. CONCLUSIONS: Based on recent CVOTs and guideline updates, the choice of add-on to metformin therapy for patients with T2DM and established CV disease should be a sodium-glucose co-transporter-2 inhibitor or a glucagon-like peptide-1 agonist with proven CV benefit. Additional treatment options for those individuals who require therapy intensification, as well as in patients with T2DM and without established CVD include DPP-4 inhibitors and SUs. Since few head-to-head trials have compared the effects of different oral glucose-lowering agents on CV outcomes in T2DM, with most CVOTs using placebo as a comparator, the CAROLINA trial will provide important information on the comparative CV safety of a commonly prescribed SU and a DPP-4 inhibitor.


Assuntos
Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/terapia , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Progressão da Doença , Hospitalização , Humanos , Medição de Risco , Fatores de Risco , Compostos de Sulfonilureia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
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