NETWORK META-ANALYSIS OF FIXED DOSE COMBINATION THERAPIES FOR THE FIRST-LINE TREATMENT OF TYPE 2 DIABETES MELLITUS
Author(s)
Jindal R, Gupta J, Arora A, Kaur M, Kumar R, Kaushik PHeron Health Pvt. Ltd., Chandigarh, India
OBJECTIVES: To assess the relative efficacy and safety of fixed dose combinations (FDCs) of anti-diabetic drugs in treatment naïve patients with type 2 diabetes mellitus (T2DM) using network meta-analysis technique. METHODS: Randomized controlled trials, evaluating FDCs in treatment naïve patients with T2DM were searched via Embase® and MEDLINE®. The abstracts were reviewed and data extractions were conducted by two independent reviewers. The outcomes of interest included reduction in Hb1Ac levels, patients with HbA1c<7%, fasting plasma glucose (FPG) levels, and incidence of hypoglycemia. A network meta-analysis using WinBUGS®was performed to combine the reported direct and indirect evidence and a probability ranking for the included combinations was generated. RESULTS: Eleven trials (n=5781 patients) comparing the following FDCs: sulfonylureas/biguanides (SUL/BGU), thiazolidinediones/biguanides (TZD/BGU), dipeptidyl peptidase-4 inhibitors/biguanides (DPP-4/BGU), alpha-glucosidase inhibitors/biguanides (AGI/BGU), and thiazolidinediones/sulfonylureas (TZD/SUL) were included. Following network meta-analysis using BGU, TZDs, and SUL as common comparators, TZD/SUL was observed to be significantly better in terms of patients with HbA1c<7% than other FDCs [relative risk; 95% credible intervals vs. SUL/BGU (1.16; 1.03-1.3), vs. TZD/BGU (1.12; 1.01-1.24), and DPP-4/BGU (1.18; 1.07-1.29)]. Statistically, however, non-significant differences were observed among the FDCs other than TZD/SUL for this outcome. All FDCs achieved clinically meaningful reductions in HbA1c and FPG, though the differences between the FDCs were statistically non-significant. According to the probability ranking for reduction in HbA1c and FPG levels, the rank favored TZD/SUL followed by AGI/BGU, TZD/BGU, SUL/BGU, and DPP/BGU. The probability of occurrence of hypoglycemia was highest with SUL/BGU (78.3%) followed by TZD/SUL (20.2%), TZD/BGU (0.03%), and DPP-4/BGU (0.005%). Incidence of hypoglycemia was not reported for AGI/BGU. CONCLUSIONS: Clinically, all FDCs effectively achieved glycemic control in patients with T2DM, however, the risk ratios from network meta-analysis were inconclusive to determine the relative efficacy of these FDCs. The probability ranking suggested the potential use of TZD/SUL in treatment naïve T2DM patients.
Conference/Value in Health Info
2012-09, ISPOR Asia Pacific 2012, Taipei, Taiwan
Value in Health, Vol. 15, No. 7 (November 2012)
Code
PDB7
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Diabetes/Endocrine/Metabolic Disorders