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Metformin Monotherapy (metformin + monotherapy)
Selected AbstractsVildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitusDIABETES OBESITY & METABOLISM, Issue 5 2009E. Bosi Aim:, To compare the efficacy and safety of vildagliptin and metformin initial combination therapy with individual monotherapies in treatment-naive patients with type 2 diabetes mellitus (T2DM). Methods:, This was a 24-week, randomized, double-blind, active-controlled study. Treatment-naive patients with T2DM who had a glycated haemoglobin (HbA1c) of 7.5,11% (N = 1179) were randomized equally to receive vildagliptin plus high-dose metformin combination therapy (50 mg + 1000 mg twice daily), vildagliptin plus low-dose metformin combination therapy (50 mg + 500 mg twice daily), vildagliptin monotherapy (50 mg twice daily) or high-dose metformin monotherapy (1000 mg twice daily). The primary objective was to demonstrate that HbA1c reduction from baseline with either combination therapy is superior to both monotherapies at the week 24 endpoint. Patients who failed glycaemic-screening criteria [HbA1c >11% or fasting plasma glucose (FPG) >15 mmol/l (270 mg/dl)] could enter a 24-week, single-arm substudy. These patients (N = 94) received open-label vildagliptin plus high-dose metformin combination therapy (100 mg + 1000 mg twice daily). Results:, From comparable baseline values (8.6,8.7%), HbA1c decreased in all four treatment groups, to the greatest extent with vildagliptin plus high-dose metformin combination therapy. Mean (SE) HbA1c change from baseline was ,1.8% (0.06%), ,1.6% (0.06%), ,1.1% (0.06%) and ,1.4% (0.06%) with vildagliptin plus high-dose metformin combination therapy, vildagliptin plus low-dose metformin combination therapy, and vildagliptin and metformin monotherapies respectively. The between-group difference was superior with vildagliptin plus high-dose metformin combination therapy (p < 0.001 vs. both monotherapies) and vildagliptin plus low-dose metformin combination therapy (p < 0.001 and p = 0.004, vs. vildagliptin and metformin monotherapies, respectively). Higher baseline HbA1c values were linked to greater HbA1c reductions, with changes of ,3.2% (0.22%), ,2.7% (0.22%), ,1.5% (0.24%) and ,2.6% (0.26%) respectively, occurring in patients with baseline HbA1c,10%. Reductions in FPG were superior with vildagliptin plus high-dose metformin combination therapy [change from baseline ,2.63 (0.13) mmol/l] compared with both monotherapies [,1.26 (0.13) mmol/l and ,1.92 (0.13) mmol/l, respectively; p < 0.001]. There was no incidence of hypoglycaemia or severe hypoglycaemia with either combination therapy, and neither was associated with weight gain. All treatments were well tolerated and displayed a comparable incidence of adverse events overall. Despite superior HbA1c lowering, the vildagliptin plus low-dose metformin combination therapy group demonstrated a favourable gastrointestinal (GI) tolerability profile compared with metformin monotherapy. Conclusions:, In treatment-naive patients, combinations of vildagliptin and both high-dose and low-dose metformin provide superior efficacy to monotherapy treatments with a comparable overall tolerability profile and low risk of hypoglycaemia. The potential dose-sparing effect of adding vildagliptin to low-dose metformin in preference to the up-titration of metformin may allow patients to achieve equivalent or superior HbA1c lowering without the GI tolerability issues associated with higher doses of metformin. [source] Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapyDIABETES OBESITY & METABOLISM, Issue 2 2009E. Ferrannini Aim:, To examine the efficacy and safety of vildagliptin vs. glimepiride as add-on therapy to metformin in patients with type 2 diabetes mellitus in a 52-week interim analysis of a large, randomized, double-blind, multicentre study. The primary objective was to demonstrate non-inferiority of vildagliptin vs. glimepiride in glycosylated haemoglobin (HbA1c) reduction at week 52. Methods:, Patients inadequately controlled on metformin monotherapy (HbA1c 6.5,8.5%) and receiving a stable dose of metformin (mean dose 1898 mg/day; mean duration of use 36 months) were randomized 1:1 to receive vildagliptin (50 mg twice daily, n = 1396) or glimepiride (titrated up to 6 mg/day; mean dose 4.5 mg/day, n = 1393). Results:, Non-inferiority of vildagliptin was demonstrated (97.5% confidence interval 0.02%, 0.16%) with a mean (SE) change from baseline HbA1c (7.3% in both groups) to week 52 endpoint of ,0.44% (0.02%) with vildagliptin and ,0.53% (0.02%) with glimepiride. Although a similar proportion of patients reached a target HbA1c level of <7% with vildagliptin and glimepiride (54.1 and 55.5%, respectively), a greater proportion of patients reached this target without hypoglycaemia in the vildagliptin group (50.9 vs. 44.3%; p < 0.01). Fasting plasma glucose (FPG) reductions were comparable between groups (mean [SE] ,1.01 [0.06] mmol/l and ,1.14 [0.06] mmol/l respectively). Vildagliptin significantly reduced body weight relative to glimepiride (mean [SE] change from baseline ,0.23 [0.11] kg; between-group difference ,1.79 kg; p < 0.001) and resulted in a 10-fold lower incidence of hypoglycaemia than glimepiride (1.7 vs. 16.2% of patients presenting at least one hypoglycaemic event; 39 vs. 554 hypoglycaemic events, p < 0.01). No severe hypoglycaemia occurred with vildagliptin compared with 10 episodes with glimepiride (p < 0.01), and no patient in the vildagliptin group discontinued because of hypoglycaemia compared with 11 patients in the glimepiride group. The incidence of adverse events (AEs), serious AEs and adjudicated cardiovascular events was 74.5, 7.1 and 0.9%, respectively, in patients receiving vildagliptin, and 81.1, 9.5 and 1.6%, respectively, in patients receiving glimepiride. Conclusions:, When metformin alone fails to maintain sufficient glycaemic control, the addition of vildagliptin provides comparable efficacy to that of glimepiride after 52 weeks and displays a favourable AE profile, with no weight gain and a significant reduction in hypoglycaemia compared with glimepiride. [source] Improved glycaemic control with metformin,glibenclamide combined tablet therapy (Glucovance®) in Type 2 diabetic patients inadequately controlled on metforminDIABETIC MEDICINE, Issue 8 2002M. Marre Abstract Aims To evaluate the efficacy and safety of two dosage strengths of a single-tablet metformin,glibenclamide (glyburide) combination, compared with the respective monotherapies, in patients with Type 2 diabetes mellitus (DM) inadequately controlled by metformin monotherapy. Methods In this 16-week, double-blind, multicentre, parallel-group trial, 411 patients were randomized to receive metformin 500 mg, glibenclamide 5 mg, metformin,glibenclamide 500 mg/2.5 mg or metformin,glibenclamide 500 mg/5 mg, titrated with the intention to achieve fasting plasma glucose (FPG) , 7 mmol/l. Results Decreases in glycated haemoglobin (HbA1c) and FPG were greater (P < 0.05) for metformin,glibenclamide 500 mg/2.5 mg (,1.20% and ,2.62 mmol/l) and 500 mg/5 mg (,0.91% and ,2.34 mmol/l), compared with metformin (,0.19% and ,0.57 mmol/l) or glibenclamide (,0.33% and ,0.73 mmol/l). HbA1c < 7% was achieved by 75% and 64% of patients receiving metformin,glibenclamide 500 mg/2.5 mg and 500 mg/5 mg, respectively, compared with 42% for glibenclamide and 38% for metformin (P = 0.001). These benefits were achieved at lower mean doses of metformin or glibenclamide with metformin,glibenclamide 500 mg/2.5 mg and 500 mg/5 mg (1225 mg/6.1 mg and 1170 mg/11.7 mg) than with glibenclamide (13.4 mg) or metformin (1660 mg). Treatment-related serious adverse events occurred in two patients receiving glibenclamide. Plasma lipid profiles were unaffected and mean changes in body weight were , 1.0 kg. Conclusions Intensive management of Type 2 DM with a new metformin,glibenclamide combination tablet improved glycaemic control and facilitated the attainment of glycaemic targets at lower doses of metformin or glibenclamide compared with the respective monotherapies, without compromising tolerability. Diabet. Med. 19, 673,680 (2002) [source] The impact of publishing medical specialty society guidelines on subsequent adoption of best practices: a case study with type 2 diabetesINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2010E. A. Huang Summary Aims:, Our goal was to determine the effect of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) consensus algorithm for the initiation and adjustment of type 2 diabetes (T2D) therapy, published in 2006, on the incidence of early metformin monotherapy (EMM), defined as the prescription of metformin and no other antidiabetic medications within 30 days of initial T2D diagnosis. Methods:, The incidence of EMM in the United States (US) from January 2005 to December 2007 was estimated using data from the i3 InVisionÔ Data Mart, an integrated database of enrolment dates, inpatient and outpatient medical claims, pharmaceutical claims, and laboratory results from a diverse group of US health plans. The trend in the incidence of EMM was analysed using joinpoint regression modelling. Results:, A statistically significant joinpoint was found in July 2006 (p < 0.05). From January 2005 to July 2006, EMM increased at an annualised rate of 15.6%. From July 2006 to December 2007, EMM increased at an annualised rate of 66.0%. Conclusions:, Our findings suggest that publication of the ADA/EASD algorithm caused a significant acceleration in the incidence of EMM. [source] Combination therapy with sulfonylureas and metformin and the prevention of death in type 2 diabetes: a nested case-control study,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2010Laurent Azoulay PhD Abstract Purpose To determine whether combination of sulfonylureas and metformin increases the risk of death from any cause in patients with type 2 diabetes. Methods A nested case-control study was conducted within a population-based cohort from the UK General Practice Research Database (GPRD). The cohort included patients over the age of 40 who were prescribed a first oral hypoglycaemic agent between 1 January 1988 and 30 June 2008. Cases included all patients who deceased during follow-up. Up to 10 controls were matched to each case on year of birth, date of cohort entry (±1 year) and duration of follow-up. Conditional logistic regression was used to estimate rate ratios (RRs) of death from any cause associated with the use of combination of sulfonylureas and metformin, relative to sulfonylurea monotherapy. Results The cohort comprised 84,231 users of oral hypoglycaemic agents, of whom 14,996 died from any cause during a mean of 4.3 years of follow-up (mortality rate 4.1 per 100 per year). Patients currently exposed to a combination of sulfonylureas and metformin were at a decreased risk of death from any cause compared to patients exposed to sulfonylurea monotherapy (adjusted RR: 0.77, 95%CI: 0.70, 0.85). Similar results were obtained for patients currently exposed to metformin monotherapy (adjusted RR: 0.70, 95%CI: 0.64, 0.75) when compared to sulfonylurea monotherapy. Patients had to be exposed to the combination therapy for at least 4 months prior to index date to experience a lower risk of mortality compared to sulfonylurea monotherapy. Conclusions The combination of sulfonylureas and metformin does not increase the risk of death. In contrast, it may moderately reduce this risk compared to sulfonylurea monotherapy. Copyright © 2010 John Wiley & Sons, Ltd. [source] A retrospective evaluation of congestive heart failure and myocardial ischemia events in 14,237 patients with type 2 diabetes mellitus enrolled in 42 short-term, double-blind, randomized clinical studies with rosiglitazonePHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 8 2008Alexander Cobitz MD Abstract Purpose Retrospectively investigate potential associations between rosiglitazone and congestive heart failure (CHF) and, separately, events of myocardial ischemia. Methods Data from 14,237 individuals in 42 short-term, double-blind, randomized studies of rosiglitazone versus placebo or active diabetes medications were analyzed across seven treatment comparisons using an exact logistic regression model, adjusted for number of major cardiovascular risk factors and duration of exposure. Results CHF incidence ranged 0,1.27% (SAEs) and 0.12,2.42% (all AEs) with rosiglitazone versus 0.07,0.75% (SAEs) and 0.25,1.36% (all AEs) with control. Higher odds ratios (95%CI) were observed for CHF SAEs with sulfonylurea- and insulin-containing combinations: rosiglitazone monotherapy versus placebo, 0.25 (<0.01,4.75); rosiglitazone monotherapy versus sulfonylurea/metformin monotherapy, 0.23 (<0.01,2.14); sulfonylurea,+,rosiglitazone versus sulfonylurea monotherapy, 0.95 (0.01,75.20); metformin,+,rosiglitazone versus metformin monotherapy, 0.60 (0.00,8.28); metformin,+,rosiglitazone versus metformin,+,sulfonylurea, 1.04 (0.39,2.86); sulfonylurea,+,metformin,+,rosiglitazone versus sulfonylurea,+,metformin, 3.15 (0.35,150.52); insulin,+,rosiglitazone versus insulin monotherapy, 1.63 (0.52,6.01). Myocardial ischemia incidence ranged 0.75,1.40% (SAEs) and 1.49,2.77% (all AEs) with rosiglitazone versus 0.21,2.04% (SAEs) and 0.56,2.38% (all AEs) with control. Each comparison had an OR >1, with wide confidence intervals generally including unity. With data pooling, more events of myocardial ischemia were observed with rosiglitazone (2.00%) versus control (1.53%) (HR 1.30, 95%CI 1.004,1.69). Conclusions CHF incidence may be greater when rosiglitazone is combined with sulfonylureas or insulin. When data were pooled, more events of myocardial ischemia were observed with rosiglitazone versus control. Final results from RECORD will allow a more rigorous evaluation of the cardiovascular safety profile. Copyright © 2008 John Wiley & Sons, Ltd. [source] Nonadherence as a predictor of antidiabetic drug therapy intensification (augmentation),PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 9 2004Dr Stephen J. Kogut MBA Abstract Purpose To determine if nonadherence with antidiabetic drug therapy is predictive of subsequent antidiabetic drug therapy intensification. Methods We conducted a retrospective cohort study examining retail pharmacy dispensings of sulfonylureas or metformin to 1067 patients having diabetes. Patients that did not receive a sufficient quantity of medication to cover at least 80% of days during the evaluation period were classified as nonadherent. Outcomes identified were increase in the dose of antidiabetic medication utilized, the addition of a second antidiabetic agent to the regimen or either. Results Among users of sulfonylurea monotherapy, those classified as nonadherent were 45% more likely to intensify therapy in subsequent months as compared with those classified as adherent (age-adjusted odds ratio (OR) 1.45; 95% confidence interval (CI) 1.06,2.00). This finding was largely driven by observed increases in dosage, which were more likely among patients classified as nonadherent (age-adjusted OR 1.48, 95%CI 1.07,2.05). Nonadherence was not found to be predictive of the subsequent addition of a second antidiabetic agent (OR 1.02; 95%CI 0.64,1.63). Overall findings were similar for the smaller sample of patients receiving metformin monotherapy, though observed differences did not achieve statistical significance. Conclusions Patients who were poorly adherent to oral antidiabetic drug therapy more frequently experienced an increase in the dose of medication prescribed, as compared to patients that were classified as adherent. This finding underscores the need for prescribers to consider nonadherence as a root cause when patients fail to achieve therapeutic goals. Copyright © 2004 John Wiley & Sons, Ltd. [source] A retrospective evaluation of congestive heart failure and myocardial ischemia events in 14,237 patients with type 2 diabetes mellitus enrolled in 42 short-term, double-blind, randomized clinical studies with rosiglitazonePHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 8 2008Alexander Cobitz MD Abstract Purpose Retrospectively investigate potential associations between rosiglitazone and congestive heart failure (CHF) and, separately, events of myocardial ischemia. Methods Data from 14,237 individuals in 42 short-term, double-blind, randomized studies of rosiglitazone versus placebo or active diabetes medications were analyzed across seven treatment comparisons using an exact logistic regression model, adjusted for number of major cardiovascular risk factors and duration of exposure. Results CHF incidence ranged 0,1.27% (SAEs) and 0.12,2.42% (all AEs) with rosiglitazone versus 0.07,0.75% (SAEs) and 0.25,1.36% (all AEs) with control. Higher odds ratios (95%CI) were observed for CHF SAEs with sulfonylurea- and insulin-containing combinations: rosiglitazone monotherapy versus placebo, 0.25 (<0.01,4.75); rosiglitazone monotherapy versus sulfonylurea/metformin monotherapy, 0.23 (<0.01,2.14); sulfonylurea,+,rosiglitazone versus sulfonylurea monotherapy, 0.95 (0.01,75.20); metformin,+,rosiglitazone versus metformin monotherapy, 0.60 (0.00,8.28); metformin,+,rosiglitazone versus metformin,+,sulfonylurea, 1.04 (0.39,2.86); sulfonylurea,+,metformin,+,rosiglitazone versus sulfonylurea,+,metformin, 3.15 (0.35,150.52); insulin,+,rosiglitazone versus insulin monotherapy, 1.63 (0.52,6.01). Myocardial ischemia incidence ranged 0.75,1.40% (SAEs) and 1.49,2.77% (all AEs) with rosiglitazone versus 0.21,2.04% (SAEs) and 0.56,2.38% (all AEs) with control. Each comparison had an OR >1, with wide confidence intervals generally including unity. With data pooling, more events of myocardial ischemia were observed with rosiglitazone (2.00%) versus control (1.53%) (HR 1.30, 95%CI 1.004,1.69). Conclusions CHF incidence may be greater when rosiglitazone is combined with sulfonylureas or insulin. When data were pooled, more events of myocardial ischemia were observed with rosiglitazone versus control. Final results from RECORD will allow a more rigorous evaluation of the cardiovascular safety profile. Copyright © 2008 John Wiley & Sons, Ltd. [source] | ||||||||||