Pioglitazone and metformin fixed-dose combination in type 2 diabetes mellitus: an evidence-based review of its place in therapy

Introduction:

Type 2 diabetes mellitus, a metabolic disease with increasing incidence, is one of the most important cardiovascular risk factors. Insulin resistance represents the common mechanism that leads to type 2 diabetes in obese subjects. Metformin and the thiazolidinediones, pioglitazone and rosiglitazone, are insulin-sensitizing agents available for treatment of type 2 diabetes. Large clinical trials have demonstrated the effectiveness of both metformin and pioglitazone in reducing cardiovascular morbidity and mortality. The fixed-dose combination of metformin and pioglitazone appears to be a good option for treating diabetes in insulin-resistant patients.

Aims:

The purpose of this article is to review the place in therapy of a fixed-dose combination of pioglitazone and metformin in the management of patients with type 2 diabetes.

Evidence review:

The current evidence suggests that combined therapy may help to achieve the recommended goals in the management of diabetes. A fixed-dose formulation of pioglitazone and metformin may provide advantages in terms of glycemic control and other cardiovascular risk factors frequently associated with diabetes.

Place in therapy:

The current evidence shows that a fixed-dose formulation of pioglitazone and metformin offers an effective option for the management of patients with type 2 diabetes when monotherapy fails in the achievement of the recommended standards of care.     

Effects of saxagliptin added to sub-maximal doses of metformin compared with uptitration of metformin in type 2 diabetes: the PROMPT study

Abstract

Objective:

The PROMPT study compared efficacy and tolerability of two treatment intensification strategies: adding saxagliptin or uptitrating metformin monotherapy, in patients with type 2 diabetes (T2D) and inadequate glycaemic control on a sub-maximal metformin dose.     

Long-term effects of pioglitazone in Japanese patients with type 2 diabetes without a recent history of macrovascular morbidity

Abstract

Objective:

To evaluate the efficacy of pioglitazone for the prevention of macrovascular outcomes in Japanese patients with type 2 diabetes, without a recent history of macrovascular morbidity.     

Efficacy and safety of linagliptin added to metformin and sulphonylurea in Chinese patients with type 2 diabetes: a sub-analysis of data from a randomised clinical trial

Abstract

Objectives:

To evaluate the efficacy and safety of linagliptin in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin and sulphonylurea.     

Initial nonadherence,primary failure and therapeutic success of metformin monotherapy in clinical practice

Abstract

Objective:

To document the extent to which drug naïve patients with diabetes continued newly initiated metformin monotherapy, and who subsequently experienced primary failure or therapeutic success.     

Vildagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus

Introduction:

Type 2 diabetes is increasing in prevalence worldwide and is a leading cause of morbidity and mortality, mainly due to the development of complications. Vildagliptin is an inhibitor of dipeptidyl peptidase 4 (DPP-4), a new class of oral antidiabetic agents.

Aims:

To evaluate the role of vildagliptin in the management of type 2 diabetes.

Evidence review:

Clear evidence shows that vildagliptin improves glycemic control (measured by glycosylated hemoglobin and blood glucose levels) more than placebo in adults with type 2 diabetes, either as monotherapy or in combination with metformin. Vildagliptin is as effective as pioglitazone and rosiglitazone, and slightly less effective than metformin, although better tolerated. Further glycemic control is achieved when adding vildagliptin to metformin, pioglitazone, or glimepride. There is evidence that vildagliptin improves beta-cell function and insulin sensitivity. Vildagliptin does not appear to be associated with weight gain or with a higher risk of hypoglycemia than placebo or other commonly used oral antidiabetic agents. Economic evidence is currently lacking.

Place in therapy:

Vildagliptin improves glycemic control with little if any weight gain or hypoglycemia in adult patients with type 2 diabetes when given alone or in combination with metformin, thiazolidinediones, or sulfonylureas. Since many diabetic patients require combination therapy, the complementary mechanism of action of vildagliptin and other commonly prescribed antidiabetic drugs represents an important new therapeutic option in diabetes management.     

Saxagliptin and metformin XR combination therapy provides glycemic control over 24 hours in patients with T2DM inadequately controlled with metformin

Abstract

Objective:

To assess 24-hour glycemic control with saxagliptin compared with placebo as add-on treatment to metformin in patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control.     

Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin

Abstract

Objective:

To evaluate efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes (T2D) with inadequate glycemic control on insulin alone or combined with metformin.     

Comparative effects of sitagliptin and metformin in patients with type 2 diabetes mellitus: a meta-analysis

Abstract

Background:

Sitagliptin has been widely used in the treatment of type 2 diabetes mellitus (T2DM); however, the therapeutic efficacy of sitagliptin remains inconclusive in randomized controlled studies on T2DM in which metformin has served as a control.     

Assessment of the pharmacokinetics of co-administered metformin and lobeglitazone,a thiazolidinedione antihyperglycemic agent,in healthy subjects

Abstract

Objective:

Lobeglitazone as a thiazolidinedione antihyperglycemic agent activates peroxisome proliferator-activated receptor (PPAR) γ and may be suitable as monotherapy or in combination with other antihyperglycemic agents. The primary objective of this study was to investigate potential pharmacokinetic interactions between lobeglitazone and metformin in healthy Korean subjects.     

Evaluation of the potential for pharmacokinetic and pharmacodynamic interactions between dutogliptin,a novel DPP4 inhibitor,and metformin,in type 2 diabetic patients

Abstract

Objective:

Dutogliptin is a novel, orally available, potent, and selective DPP4 inhibitor that improves glycemic control in type 2 diabetic patients. The objective of this study was to evaluate the potential pharmacokinetic and pharmacodynamic interactions, as well as the tolerability, of dutogliptin and metformin alone and in combination in type 2 diabetic patients.     

Focus on agomelatine

Abstract

Background:

Agomelatine is a novel antidepressant with agonist activity at melatonin receptors (MT₁ and MT₂), and antagonistic effects at the 5HT_2c serotonin receptor.     

Comparison of the diabetes guidelines from the ADA/EASD and the AACE/ACE

Objective

To compare recent diabetes guideline updates from the American Diabetes Association–European Association for the Study of Diabetes (ADA/EASD) and the American Association of Clinical Endocrinologists–American College of Endocrinology (AACE/ACE).

Verapamil decreases the glucose-lowering effect of metformin in healthy volunteers

Aim

The organic cation transporter 1 (OCT1) plays a key role in the cellular transport of metformin and its subsequent glucose-lowering effect. A recent non-clinical study reported that metformin uptake into hepatocytes is regulated via OCT1, and that uptake was strongly inhibited by verapamil. Therefore, we investigated the effects of verapamil co-administration on the pharmacokinetics and pharmacodynamics of metformin in humans.

Methods

We evaluated the pharmacokinetics and the anti-hyperglycaemic effects of metformin using an oral glucose tolerance test (OGTT) in 12 healthy participants, before (day 1) and after metformin treatment (day 2), and again on days 15 and 16 after co-administration with verapamil.

Results

Verapamil inhibited the ability of metformin to reduce maximum blood glucose concentrations (ΔG_max) by 62.5% (P = 0.008) and decreased the area under the glucose concentration–time curve (ΔAUC_gluc) by 238% (P = 0.015). However, verapamil did not significantly alter the C_max and the AUC of metformin, nor its renal clearance.

Conclusions

Our results suggest that verapamil remarkably decreases the glucose-lowering effect of metformin, possibly by acting as a competitive inhibitor of OCT1.     

Could FEV1 decline have a role in daily clinical practice for asthma monitoring?

Abstract

Objective:

The aim of this review was to understand whether FEV₁ decline measured during the follow-up of asthmatic subjects (FEV₁ variation between two different measurements at a distance of at least 5 years) may have a role in their management.     

Clinical inertia in the treatment of hyperglycemia in type 2 diabetes patients in primary care

Abstract

Objective:

To assess clinical inertia, defined as failure to intensify antidiabetic treatment of patients who have not achieved the HbA_1c therapeutic goal (≤7%).     

Glycemic effectiveness and medication adherence with fixed-dose combination or coadministered dual therapy of antihyperglycemic regimens: a meta-analysis

Abstract

Objectives:

To compare effects of fixed-dosed combinations (FDCs) and coadministered dual therapy (CDT) of antihyperglycemic agents on glycemic control (i.e., HbA_1c) and medication adherence.     

GLP-1 receptor agonists and HBA1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials

Abstract

Objective:

Glucagon-like peptide-1 (GLP-1) receptor agonists are available for the treatment of type 2 diabetes. We assessed the efficacy of exenatide and liraglutide to reach the HbA_1c target of <7% in people with type 2 diabetes.     

Efficacy and safety of add on therapy of bromocriptine with metformin in Indian patients with type 2 diabetes mellitus: A randomized open labeled phase IV clinical trial

Objective:

To compare the effectiveness and safety of add on therapy of bromocriptine with metformin in type 2 diabetes mellitus (DM) patients.

Material and Methods:

Adult type 2 DM patients fulfilling the inclusion criteria were randomized in three groups. Group A received metformin (1000 mg/ day), while group B patients were treated with metformin (1000 mg/day) plus bromocriptine (0.8 mg/day) and group C received metformin (1000 mg/day) plus bromocriptine (1.6 mg/day) for 12 weeks. Fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), and body weight were measured at week 4, 8, and 12 visits and glycosylated hemoglobin (HbA_1C) at week 12 visit.

Results:

Metformin alone and in combination with bromocriptine in escalating dose (0.8 mg/day and 1.6 mg/day) significantly (P < 0.05) decreased FPG and PPPG levels at weeks 4, 8, and 12 compared with pretreatment values. HbA_1C level in all three treatment groups significantly (P < 0.05) decreased at week 12 as compared with pretreatment baseline value. HbA_1C level in groups B and C significantly (P < 0.05) decreased as compared with group A at week 12. Addition of bromocriptine to metformin also significantly (P < 0.05) decreased FPG and PPPG levels in a dose-dependent manner as compared with metformin alone. Intergroup analysis did not show any statistically significant change in weight of study subjects at different intervals.

Conclusion:

The combination of bromocriptine with metformin significantly decreased FPG, PPPG, and HbA_1C compared with metformin alone in type 2 DM patients in a dose-dependent manner.KEY WORDS: Bromocriptine, diabetes mellitus, metformin