Table 1.

Summary of representative clinical findings on the regulation of sarcopenic parameters by major anti‐diabetic drugs

Anti‐diabetic drugs	Mechanism of action on muscle	Study design	Effect on muscle mass/performance	Methods/criteria for sarcopenic assessment	Effect on body weight	Effect on fat mass	Refs
Insulin	Increasing protein synthesis in muscle	Retrospective observational study	Attenuate the decline of muscle strength in the lower extremities	SMI and GS were used to assess sarcopenia	Weight increase	Increase of both FM and FFM	24
		Population‐based KORA‐Age study	Preserve muscle mass, but not muscle function	SMI, hand grip strength, a timed up and go test			25
Sulfonylureas and glinides (glibenclamide, repaglinide)	Inhibiting ATP‐sensitive potassium channel and increasing caspase‐3 activity in the skeletal muscle	Database‐searching study	Muscle atrophy was found in 0.27% of glibenclamide reports within 8 months				33
		Post hoc analysis	24 week treatment of glimepiride induced none significant decrease in muscle mass in T2DM patients	FBFM			34
Metformin	Increasing AMPKα2 activity in the skeletal muscle; inhibiting mTORC1	Randomized clinical trial in newly diagnosed T2DM patients				Significant decrease in per cent body fat and body fat mass	39
		Multicentre longitudinal cohort study	Insulin sensitizers may attenuate muscle loss	Total lean and appendicular lean mass was derived from dual X‐ray absorptiometry scans			41
		Placebo‐controlled clinical trial (850 mg of metformin or a placebo twice a day for 2 months)	Increase in lean weight	Body mass index and waist/hip ratio			38
Thiazolidinedione (rosiglitazone, pioglitazone)	Activating PPAR‐γ; decreasing muscle lipid content and increasing muscle mass; inducing oxidative stress	A multicentre longitudinal cohort study	Attenuate muscle loss	Total lean and appendicular lean mass was derived from dual X‐ray absorptiometry scans		No change/sight decrease/increase in FM	41
		Older (65–79 years) non‐diabetic overweight/obese men and women undergoing weight‐loss training	Pioglitazone increased visceral fat loss but did not reduce skeletal muscle loss	Lean mass was measured using dual X‐ray absorptiometry			93
GLP‐1 analogues (exenatide, liraglutide)	Increasing insulin secretion; decreasing the loss of FFM; decreasing protein degradation	T2DM patients treated with metformin and other oral anti‐diabetic drugs except for thiazolidinediones	Total lean mass was significantly reduced from baseline		Weight loss	Decrease in FM	59
		Perspective study carried out in overweight and obese T2DM patients (metformin and liraglutide)	Induce an increase in SMI and preserve the muscular tropism	SMI			62
		T2DM patients on haemodialysis, who had been treated with insulin and newly added teneligliptin or dulaglutide	Dulaglutide significantly decreased SMM	SMM			63
DPP‐IV inhibitor (sitagliptin, vildagliptin, saxagliptin)	Increasing GLP‐1 concentration and decreasing muscle lipid content	Retrospective observational study with 105 T2DM patients	Prevent the progressive loss of muscle mass with ageing in patients with T2DM.	SMI	No significant effect	Unclear	65
		Elderly T2DM patients	Induce better sarcopenic parameters	Fat‐free mass, skeletal muscle mass, and related indices, muscle strength, and gait speed			66
SGLT2 inhibitor (dapagliflozin, canagliflozin, tofogliflozin, luseogliflozin)	Inhibiting inflammatory cytokines, macrophage aggregation; increasing muscle contractility and muscle mass	Post hoc analysis of a prospective, single‐centre, open‐label, single‐arm study with patients receiving ipragliflozin for 24 weeks	Lean mass was significantly decreased in ipragliflozin group but not the ipragliflozin + metformin group		Weight loss	Decrease in FM	80
		Single‐arm, single‐centre, open‐label study	A significant reduction in lean mass				81

DPP‐IV, dipeptidyl peptidase IV; FBFM, fat and bone‐free mass; FFM, fat‐free mass; FM, fat mass; GLP‐1, glucagon‐like peptide‐1; GS, grip strength; SGLT2, sodium‐glucose co‐transporter 2; SMI, skeletal muscle index; SMM, skeletal muscle mass; T2DM, type 2 diabetes mellitus.