. 2021 May 8;81(9):1003–1030. doi: 10.1007/s40265-021-01499-w

Table 1.

Overview of the drug-drug interaction studies with oral semaglutide

Population	Design	Perpetrator drug	Victim drug	Exposure	ETR (90% CI)	No effect interval
Studies with oral semaglutide as the perpetrator drug
32 healthy subjects	Open-label, single sequence crossover trial [42]	Oral semaglutide 20 mg at steady state	Metformin 850 mg BID for 4 days	AUC_0-12h	1.32 (1.23, 1.43)	0.80 to 1.25
			Metformin 850 mg BID for 4 days	C_max	0.98 (0.90, 1.06)	0.80 to 1.25
			Digoxin 500 μg single dose	AUC_0-inf	1.03 (0.96, 1.11)	0.80 to 1.25
			Digoxin 500 μg single dose	C_max	0.98 (0.89, 1.09)	0.80 to 1.25
52 healthy subjects	Open-label, single sequence crossover trial [42]	Oral semaglutide 20 mg at steady state	Lisinopril 20 mg single dose	AUC_0-inf	1.07 (0.99, 1.15)	0.80 to 1.25
			Lisinopril 20 mg single dose	C_max	0.96 (0.88, 1.06)	0.80 to 1.25
			S-warfarin 25 mg single dose	AUC_0-inf	1.08 (1.04, 1.12)	0.80 to 1.25
			S-warfarin 25 mg single dose	C_max	0.88 (0.83, 0.94)	0.80 to 1.25
41 healthy subjects	Open-label, single sequence crossover trial [43]	Oral semaglutide 14 mg at steady state	Furosemide 40 mg single dose	AUC_0-inf	1.28 (1.16, 1.42)	0.80 to 1.25
			Furosemide 40 mg single dose	C_max	0.66 (0.53, 0.82)	0.80 to 1.25
			Rosuvastatin 20 mg single dose	AUC_0-inf	1.41 (1.24, 1.60)	0.80 to 1.25
			Rosuvastatin 20 mg single dose	C_max	1.10 (0.94, 1.28)	0.80 to 1.25
25 post-menopausal females	Open-label, single sequence crossover trial [44]	Oral semaglutide 14 mg at steady state	Levonorgestrel 0.15 mg for 8 days	AUC_0-24h	1.06 (0.97, 1.17)	0.80 to 1.25
			Levonorgestrel 0.15 mg for 8 days	C_max	0.95 (0.87, 1.05)	0.80 to 1.25
			Ethinylestradiol 0.03 mg for 8 days	AUC_0-24h	1.06 (1.01, 1.10)	0.80 to 1.25
			Ethinylestradiol 0.03 mg for 8 days	C_max	0.97 (0.90, 1.05)	0.80 to 1.25
45 healthy subjects	Open-label, one-sequence crossover, two-part trial [32]	Oral semaglutide 14 mg at steady state	Levothyroxine 600 μg single dose	_bcAUC_0-24h,T4	1.33 (NR)	0.80 to 1.25
45 healthy subjects	Open-label, one-sequence crossover, two-part trial [32]	Oral semaglutide 14 mg at steady state	Levothyroxine 600 μg single dose	_bcC_max,T4	NR	0.80 to 1.25
Studies with oral semaglutide as the victim drug
45 healthy subjects	Open-label, one-sequence crossover, two-part trial [32]	Five placebo tablets OD for 5 weeks	Oral semaglutide 14 mg at steady state	AUC_0-24h	0.66 (NR)	0.70 to 1.43
45 healthy subjects	Open-label, one-sequence crossover, two-part trial [32]	Five placebo tablets OD for 5 weeks	Oral semaglutide 14 mg at steady state	C_max	0.68 (NR)	0.70 to 1.43
54 healthy subjects	Randomized, open-label, parallel-group trial [34]	Omeprazole 40 mg OD for 10 days	Oral semaglutide 5–10 mg for 10 days	AUC_0-24h,Day10	1.13 (0.88, 1.45)	0.68 to 1.46
54 healthy subjects	Randomized, open-label, parallel-group trial [34]	Omeprazole 40 mg OD for 10 days	Oral semaglutide 5–10 mg for 10 days	C_max,Day10	1.16 (0.90, 1.49)	0.68 to 1.46

AUC area under the concentration time curve, bc baseline corrected, BID twice daily, C_max maximum plasma concentration, ETR estimated treatment ratio, Inf infinity, NR not reported, OD once daily, T4 total thyroxine