Table 4.

Effect of antihyperglycaemic drugs on GLP‐1

Study (population)	Duration	GLP‐1 levels	Mechanism
Metformin
Kappe et al 2013113 (murine GLUTag cell line)	Acute: 0.5 mmol/L for 30 min Long‐term: 0.5 mmol/L for 48 h	Acute: GLP‐1→ Long‐term: GLP‐1↑ Preproglucagon ↓	Metformin direct effect on GLP‐1 secretion
Kim et al 201483 (hyperglycaemic db/db mice)	8 wk	GLP‐1↑ in serum GLP‐1 receptor expression in islets ↑	Metformin direct effect on GLP‐1 secretion
Pyra et al 2012103 (human enteroendocrine cells NCI‐H716)	Cells were incubated for 2 h at 37°C	GLP‐1↑	Metformin direct effect on GLP‐1 secretion
SGLT1/2 inhibitors
Powell et al 201386 (high‐fat diet mice)	Single dose	Total and active GLP‐1↑	SGLT1 inhibition
Zambrowicz et al 2013114 (Healthy subjects)	12 d	Total and active GLP‐1↑	SGLT1 inhibition
Zambrowicz et al 2013115 (Patients with T2DM)	Single dose	Total and active GLP‐1↑	SGLT1 inhibition
Oguma et al 201587 (Zucker diabetic fatty rats)	Single dose	Active GLP‐1↑	SGLT1 inhibition
Ferrannini et al 201488 (Patients with T2DM)	4 weeks	GLP‐1↑	Unknown
α‐GIs
Hamada et al 2013116 (Male Nagoya‐Shibata‐Yasuda (NSY) mice)	4 or 12 wk	Active GLP‐1↑	α‐GI enhancement of bile acid levels
Lee et al 201591 (Kir6.2 knockout mice)	Early phase: 5 min Late phase: 10 and 30 min	Active GLP‐1↑	α‐GIs delay carbohydrate absorption and potentiate GLP1 secretion. Miglitol activates duodenal EC cells, possibly via SGLT3, & potentiates GLP1 secretion via parasympathetic nervous system
Zheng et al 2013117 (Patients with T2DM)	24 wk	GLP‐1↑	Large amounts of undigested carbohydrates reach the lower portion of the small intestine which is rich in L cells
Amagai et al 2017118 (Suspected late dumping syndrome patients)	Single dose	Total GIP↓ Active GLP‐1↓ in early phase	Inhibiting absorption of carbohydrates in the upper gastrointestinal tract
Pioglitazone
Zheng et al 201792 (Sprague Dawley rats)	14 wk	Active GLP‐1↑	Improving insulin resistance