Effectiveness and safety of glimepiride and iDPP4, associated with metformin in second line pharmacotherapy of type 2 diabetes mellitus: systematic review and meta‐analysis

Abstract

SummaryObjectiveOur review analyses the studies that have specifically compared the association iDPP4/metformin with glimepiride/metformin, both in second line pharmacotherapy of type 2 diabetes mellitus (DM2).MethodsSystematic literature review with a meta‐analysis of clinical trials comparing glimepiride with any iDPP4, both used together with metformin as a second line treatment of DM2. The effectiveness variables used were as follows: %HbA1c variation, fasting plasma glucose variation, patients achieving the therapeutic objective of HbA1c <7%, treatment dropouts due to lack of effectiveness and rescue treatments needed. The safety variables included were as follows: weight variation at the end of treatment; presentation of any type of adverse event; presentation of serious adverse events; patients who experienced any type of hypoglycaemia; patients who experienced severe hypoglycaemia; treatments suspended due to adverse effects; and deaths for any reason.ResultsFour studies met the inclusion criteria. The group treated with glimepiride showed better results in all effectiveness variables. Regarding safety variables, the main differences observed were in the greater number of cases with hypoglycaemia in the group treated with glimepiride, and the serious adverse events or treatment discontinuations due to these which occurred in slightly over 2% more cases in this group compared to the iDPP4 group. The remaining adverse events, including mortality, did not show any differences between both groups. The variation in the weight difference between groups (2.1 kg) is not considered clinically relevant.ConclusionsA greater effectiveness is seen in the glimepiride/metformin association, which should not be diminished by slight differences in adverse effects, with absence of severe hypoglycaemia in over 98% of patients under treatment. The association of glimepiride/metformin, both due to cost as well as effectiveness and safety, may be the preferential treatment for most DM2 patients, and it offers a potential advantage in refractory hyperglycemic populations, tolerant to treatment.

Combination Therapy of Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus

“…Several meta-analyses compared SU and DPP4i as an add-on therapy to metformin [ 6 7 8 9 10 11 ]. DPP4i lowered HbA1c levels to a similar extent [ 6 7 ] or slightly less (HbA1c difference 0.08% to 0.21%) [ 8 9 11 ] compared to SU when added to metformin ( Table 1 ). A meta-analysis comparing DPP4i with SU as an add-on therapy to metformin showed a significantly greater reduction in HbA1c from baseline to 12 weeks with SU versus DPP4i (mean difference, 0.21%) but no significant difference at 52 and 104 weeks [ 7 ].…”

Comparative evaluation of safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus: Indian multicentric randomized trial - START Study

“…This study suggested that there is greater effectiveness with the glimepiride/metformin combination with good safety profile, which makes it a preferential choice of treatment for many uncontrolled T2DM patients. [ 24 ]…”

Combination therapy of oral hypoglycemic agents in patients with type 2 diabetes mellitus

“…Several meta-analyses compared SU and DPP4i as an add-on therapy to metformin [ 6 - 11 ]. DPP4i lowered HbA1c levels to a similar extent [ 6 , 7 ] or slightly less (HbA1c difference 0.08% to 0.21%) [ 8 , 9 , 11 ] compared to SU when added to metformin ( Table 1 ).…”