Alogliptin + metformin combination for the treatment of type 2 diabetes mellitus

Abstract

The impact of type 2 diabetes mellitus continues to grow worldwide, with appropriate glycemic management being a cornerstone of treatment to minimize the risk of macrovascular and microvascular complications. While metformin is widely utilized as a first-line agent for patients without a contraindication to therapy, treatment guidelines recommend a variety of options for second-line dual therapy with patient-specific choices depending on assessment of hypoglycemia risk, weight effects, tolerability, cost and other considerations. Incretin-based therapies, inclusive of dipeptidyl peptidase-4 inhibitors, have become a widely utilized group of medications due to their potentially advantageous effects, such as a low risk of hypoglycemia and overall favorable tolerability profile. Accordingly, fixed-dose combination products containing metformin in combination with a dipeptidyl peptidase-4 inhibitor have been developed by several manufacturers. This article summarizes the current evidence for the safety and efficacy of alogliptin and metformin used in combination for the treatment of type 2 diabetes mellitus.

KEYWORDS:

• Alogliptin
• diabetes mellitus
• DPP-4 inhibitor
• fixed-dose combination
• incretin effect
• kazano
• metformin

Financial & competing interests disclosure

JJ. Neumiller receives institutional research grant support from AstraZeneca, Johnson & Johnson, Merck, and Novo Nordisk. JJ. Neumiller has advisory Board Membership for Sanofi and Janssen Pharmaceuticals and serves on speaker bureaus for Novo Nordisk and Janssen Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The incretin effect is mediated by the hormones released from the digestive tract, and results in increased insulin response to oral versus parenteral nutrient intake.

• The incretin hormone GLP-1, which stimulates glucose-dependent insulin production and suppresses inappropriate glucagon release, is rapidly metabolized by the dipeptidyl-peptidase-4 enzyme.

• The metformin plus alogliptin fixed-dose combination product contains the highly selective dipeptidyl-peptidase-4 inhibitor alogliptin with metformin, offering a reduced pill burden with complementary glucose-lowering mechanisms.

• The combination of metformin plus alogliptin has been studied as alogliptin add-on to patients inadequately controlled on metformin monotherapy and as initial combination therapy in drug-naïve T2DM patients.

• The combination of alogliptin and metformin was generally well tolerated in clinical trials, with the most common side effects reported being upper respiratory tract infection, nasopharyngitis, diarrhea, hypertension, headache, back pain and urinary tract infection.

• Key warnings and precautions listed in the prescribing information include lactic acidosis, acute pancreatitis, hypersensitivity, hepatic effects, radiologic studies with contrast and vitamin B₁₂ deficiency.

• Cardiovascular outcome data with alogliptin reported no increased risk of hospitalization for heart failure or for a composite outcome consisting of major adverse cardiovascular events.