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

• DOI: 10.1186/s12933-018-0663-6
• Publication Date: 2018-01-24T08:12:24Z
• 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
• Keywords: Adult; Male; Time Factors; Databases, Factual; Taiwan; Administration, Oral; Risk Assessment; 03 medical and health sciences; 0302 clinical medicine; Risk Factors; Diseases of the circulatory (Cardiovascular) system; Humans; Hypoglycemic Agents; Glycoside Hydrolase Inhibitors; Original Investigation; Aged; Retrospective Studies; Type 2 diabetes; Middle Aged; Cardiovascular risk; Metformin; 3. Good health; Diabetes Mellitus, Type 2; Cardiovascular Diseases; RC666-701; Anti-diabetic agent; Drug Therapy, Combination; Female; Thiazolidinediones

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