Comparison of the efficacy of anti-diabetic medications as add-on to metformin in type 2 diabetes mellitus from a real-world database

Ryosuke Ono; Chika Ogami; Chihiro Hasegawa; Hideto To; Yoshiaki Matsumoto; Yasuhiro Tsuji

doi:10.1186/s40360-023-00716-4

Comparison of the efficacy of anti-diabetic medications as add-on to metformin in type 2 diabetes mellitus from a real-world database

BMC Pharmacol Toxicol. 2023 Dec 9;24(1):75. doi: 10.1186/s40360-023-00716-4.

Authors

Ryosuke Ono^{1

2}, Chika Ogami³, Chihiro Hasegawa¹, Hideto To³, Yoshiaki Matsumoto¹, Yasuhiro Tsuji⁴

Affiliations

¹ Laboratory of Clinical Pharmacometrics, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan.
² Clinical Pharmacology and Bioanalytics, Pfizer R&D Japan, 3-22-7 Yoyogi, Shibuya-Ku, Tokyo, 151-8589, Japan.
³ Department of Medical Pharmaceutics, Graduate School of Medical and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, 930-0194, Japan.
⁴ Laboratory of Clinical Pharmacometrics, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan. tsuji.yasuhiro@nihon-u.ac.jp.

Abstract

Background: Metformin is recommended as a first-line drug in the guidelines of the treatment for type 2 diabetes mellitus. However, high-quality evidence from clinical trials directly comparing the degree of hypoglycemic effect of combination therapy of metformin and a hypoglycemic agent with a different mechanism of action with that of monotherapy of a hypoglycemic drug is lacking. We aimed to examine whether combination therapy of hypoglycemic agents with metformin showed antagonism, addition, or synergism compared to monotherapy with hypoglycemic agents other than metformin regarding hemoglobin A_1c levels.

Methods: This retrospective cohort study used a medical information database in Japan. Non-insulin anti-hyperglycemic agents with different mechanisms of action were classified into eight drug classes. A monotherapy cohort and a combination therapy added to the metformin cohort were defined. The change in hemoglobin A_1c levels was evaluated to compare the treatment effect between the cohorts.

Results: A total of 13,359 patients with type 2 diabetes mellitus in the monotherapy cohort and 1,064 in the metformin combination therapy cohort were identified. A comparison of the change from baseline HbA1c level by drug class between the two cohorts showed a similar trend. Among those treated with dipeptidyl peptidase-4 inhibitor and sodium-glucose co-transporter-2 inhibitor, no clinically significant difference was observed between the two cohorts (0.00% and -0.07% for unadjusted, 0.15% and -0.03% for propensity score matching-adjusted, and 0.09% and -0.01% for inverse probability treatment weighting-adjusted analysis).

Conclusions: According to the results of this study, the effect of dipeptidyl peptidase-4 inhibitor or sodium-glucose co-transporter-2 inhibitor added to metformin seems to be additive with respect to the reduction in hemoglobin A_1c.

Keywords: Dipeptidyl peptidase-4 inhibitor; HbA1c; Hypoglycemic agents; Interaction of metformin; Monotherapy; Sodium-glucose co-transporter-2 inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blood Glucose
Diabetes Mellitus, Type 2* / drug therapy
Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / therapeutic use
Drug Therapy, Combination
Glucose
Glycated Hemoglobin
Humans
Hypoglycemic Agents / pharmacology
Metformin* / therapeutic use
Retrospective Studies
Sodium / therapeutic use
Sodium-Glucose Transporter 2 Inhibitors*
Symporters* / therapeutic use
Treatment Outcome

Substances

Metformin
Hypoglycemic Agents
Dipeptidyl-Peptidase IV Inhibitors
Glycated Hemoglobin
Sodium-Glucose Transporter 2 Inhibitors
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Symporters
Glucose
Sodium
Blood Glucose