Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study.

Abstract

OBJECTIVE:

Metformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA) remains unclear. We investigated the cardiovascular risk of various ADAs used as add-on medication to metformin in T2DM patients from a nationwide cohort.

METHODS:

T2DM patients using different add-on oral ADAs after an initial metformin therapy of > 90 days were identified from the Taiwan National Health Insurance Database. Five classes of ADAs, including sulphonylureas (SU), glinides, thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), and dipeptidyl peptidase-4 inhibitors (DPP-4I) were selected for analysis. The reference group was the SU added to metformin. Patients were excluded if aged < 20 years, had a history of stroke or acute coronary syndrome (ACS), or were receiving insulin treatment. The primary outcomes included any major adverse cardiovascular event (MACE) including ACS, ischemic/hemorrhagic stroke, and death. A Cox regression model was used to estimate the hazard ratio (HR) for MACE.

RESULTS:

A total of 26,742 patients receiving their add-on drug to metformin of either SU (n = 24,277), glinides (n = 962), TZD (n = 581), AGI (n = 808), or DPP-4I (n = 114) were analyzed. After a mean follow-up duration of 6.6 ± 3.4 years, a total of 4775 MACEs occurred. Compared with the SU+metformin group (reference), the TZD+metformin (adjusted HR: 0.66; 95% CI 0.50-0.88, p = 0.004) and AGI+metformin (adjusted HR: 0.74; 95% CI 0.59-0.94, p = 0.01) groups showed a significantly lower risk of MACE.

CONCLUSION:

Both TZD and AGI, when used as an add-on drug to metformin were associated with lower MACE risk when compared with SU added to metformin in this retrospective cohort study. Trial registration CE13152B-3. Registered 7 Mar, 2013, retrospectively registered.

• Authors: Cheng-Wei Chan, Chu-Leng Yu, Jiunn-Cherng Lin, Yu-Cheng Hsieh, Che-Chen Lin, Chen-Ying Hung, Cheng-Hung Li, Ying-Chieh Liao, Chu-Pin Lo, Jin-Long Huang, Ching-Heng Lin, Tsu-Juey Wu
• Journal: Cardiovascular diabetology (Cardiovasc Diabetol) Vol. 17 Issue 1 Pg. 20 (01 24 2018) ISSN: 1475-2840 [Electronic] England
• PMID: 29368615 (Publication Type: Comparative Study, Journal Article, Observational Study, Research Support, Non-U.S. Gov't)

Chemical References

• Glycoside Hydrolase Inhibitors
• Hypoglycemic Agents
• Thiazolidinediones
• Metformin

Topics

• Administration, Oral
• Adult
• Aged
• Cardiovascular Diseases (diagnosis, epidemiology, prevention & control)
• Databases, Factual
• Diabetes Mellitus, Type 2 (diagnosis, drug therapy, epidemiology)
• Drug Therapy, Combination
• Female
• Glycoside Hydrolase Inhibitors (administration & dosage, adverse effects)
• Humans
• Hypoglycemic Agents (administration & dosage, adverse effects)
• Male
• Metformin (administration & dosage, adverse effects)
• Middle Aged
• Retrospective Studies
• Risk Assessment
• Risk Factors
• Taiwan (epidemiology)
• Thiazolidinediones (administration & dosage, adverse effects)
• Time Factors
• Treatment Outcome