Efficacy and tolerability of the DPP-4 inhibitor alogliptin combined with pioglitazone, in metformin-treated patients with type 2 diabetes.

Abstract

CONTEXT:

Optimal management of type 2 diabetes remains an elusive goal. Combination therapy addressing the core defects of impaired insulin secretion and insulin resistance shows promise in maintaining glycemic control.

OBJECTIVE:

The aim of the study was to assess the efficacy and tolerability of alogliptin combined with pioglitazone in metformin-treated type 2 diabetic patients.

DESIGN, SETTING, AND PATIENTS:

We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-arm study in patients with type 2 diabetes.

INTERVENTIONS:

The study consisted of 26-wk treatment with alogliptin (12.5 or 25 mg qd) alone or combined with pioglitazone (15, 30, or 45 mg qd) in 1554 patients on stable-dose metformin monotherapy (≥1500 mg) with inadequate glycemic control.

MAIN OUTCOME MEASURE:

The primary endpoint was change in glycosylated hemoglobin (HbA(1c)) from baseline to wk 26. Secondary endpoints included changes in fasting plasma glucose and β-cell function. Primary analyses compared pioglitazone therapy [all doses pooled, pioglitazone alone (Pio alone); n = 387] with alogliptin 12.5 mg plus any dose of pioglitazone (A12.5+P; n = 390) or alogliptin 25 mg plus any dose of pioglitazone (A25+P; n = 390).

RESULTS:

When added to metformin, the least squares mean change (LSMΔ) from baseline HbA(1c) was -0.9 ± 0.05% in the Pio-alone group and -1.4 ± 0.05% in both the A12.5+P and A25+P groups (P < 0.001 for both comparisons). A12.5+P and A25+P produced greater reductions in fasting plasma glucose (LSMΔ = -2.5 ± 0.1 mmol/liter for both) than Pio alone (LSMΔ = -1.6 ± 0.1 mmol/liter; P < 0.001). A12.5+P and A25+P significantly improved measures of β-cell function (proinsulin:insulin and homeostasis model assessment of β-cell function) compared to Pio alone, but had no effect on homeostasis model assessment of insulin resistance. The LSMΔ body weight was 1.8 ± 0.2, 1.9 ± 0.2, and 1.5 ± 0.2 kg in A12.5+P, A25+P, and Pio-alone groups, respectively. Hypoglycemia was reported by 1.0, 1.5, and 2.1% of patients in the A12.5+P, A25+P, and Pio-alone groups, respectively.

CONCLUSIONS:

In type 2 diabetic patients inadequately controlled by metformin, the reduction in HbA(1c) by alogliptin and pioglitazone was additive. The decreases in HbA(1c) with A12.5+P and A25+P were similar. All treatments were well tolerated.

• Authors: R A DeFronzo, C F Burant, P Fleck, C Wilson, Q Mekki, R E Pratley
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 97 Issue 5 Pg. 1615-22 (May 2012) ISSN: 1945-7197 [Electronic] United States
• PMID: 22419732 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Piperidines
• Thiazolidinediones
• Uracil
• Metformin
• alogliptin
• Pioglitazone

Topics

• Adult
• Aged
• Blood Glucose
• Diabetes Mellitus, Type 2 (drug therapy)
• Double-Blind Method
• Drug Therapy, Combination (adverse effects)
• Female
• Humans
• Hypoglycemic Agents (administration & dosage, adverse effects, therapeutic use)
• Male
• Metformin (administration & dosage, therapeutic use)
• Middle Aged
• Pioglitazone
• Piperidines (administration & dosage, adverse effects, therapeutic use)
• Thiazolidinediones (administration & dosage, therapeutic use)
• Uracil (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)