Comparison of gliclazide vs linagliptin on hypoglycemia and cardiovascular events in type 2 diabetes mellitus: A systematic review

Table 1 Inclusion and exclusion criteria of the records included in the systematic review

Inclusion criteria	Exclusion criteria
Age 19 yr and < 70 yr; Male and Female; type 2 diabetes	Age below 19 yr or ≥ 70 yr; type 1 diabetes; no diabetes
Human studies: Any race, ethnicity	Clinical trials evaluating gliclazide or linagliptin in patients with specific comorbidites including CVD1
Randomized clinical trials on safety of:	Review articles, systematic reviews and meta-analysis, network meta-analysis, pooled analysis of trials, case studies, non-randomized trials
-Gliclazide monotherapy versus linagliptin monotherapy
-Gliclazide + metformin versus linagliptin + metformin
Randomized clinical trials on safety of:	Pharmacokinetic, pharmacodynamic and bioequivalence study; retrospective chart review; observational real-world study; case study; trials studying mechanism of action of gliclazide or linagliptin; literature reporting only study design; trial summaries and implications; animal studies; preclinical studies
-Gliclazide versus DPP4 inhibitors
-Linagliptin versus sulfonylureas
Randomized clinical trials on gliclazide or linagliptin monotherapy evaluating the following outcomes:	Clinical trials evaluating gliclazide or linagliptin versus PBO
-Hypoglycemia or low blood sugar	Clinical trials evaluating gliclazide or linagliptin in combination with other GLDs except metformin
-Occurrence of 3 point major adverse cardiovascular events (3P-MACE): Cardiovascular death, nonfatal myocardial infarction/ischemia/acute coronary syndrome, or nonfatal stroke (transient ischemic attack included)	Clinical trials evaluating gliclazide or linagliptin versus other GLDs except: (1) DPP4 inhibitors for gliclazide; and (2)sulfonylureas for linagliptin
	Clinical trials evaluating other glycemic, cardiac, cardiovascular outcomes than those of interest; other outcomes (e.g., microvascular complications)

¹History of myocardial infarction, stroke, unstable angina, transient ischemic attack, percutaneous coronary intervention for coronary occlusion or coronary artery bypass graft.

Note: Efficacy was synthesized from the gliclazide and linagliptin studies that met the inclusion criteria. CVD: Cardiovascular disease; DPP4: Dipeptidyl peptidase-4; GLD: Glucose-lowering drugs; PBO: Placebo.