Practical guide: Glucagon-like peptide-1 and dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus

Table 4 Pharmacokinetic properties and renal outcomes of clinical trials with glucagon-like peptide-1 receptor agonists

Drug	Dose	Half-life (h)	Elimination	Clinical study	Renal benefit
Short-acting GLP-1 receptor agonists
Exenatide	5-10 μg twice-daily SC	2.4	Mostly renal	None	None
Lixisenatide	10-20 μg once-daily SC	3.0	Mostly renal	ELIXA[65]	Lower rate of increase in urinary albumin-to-creatinine ratio
Long-acting GLP-1 receptor agonists
Exenatide	2 mg QW SC	2.4	Mostly renal
Liraglutide	0.6 mg, 1.2 mg or 1.8 mg once-daily SC	11.6-13.0	Peptidases and renal 6%; feces 5%	LEADER[64]	Nephropathy was decreased. UACR was decreased. RAS hormone was decreased. Progression to macroalbuminuria was decreased. Doubling of serum creatinine levels was decreased. eGFR of ≤ 45 mL/min per 1.73 m2 was decreased. The initiation of renal replacement therapy was decreased. Risk of end-stage renal disease or renal death was decreased. Plasma renin concentration, renin activity, and angiotensin II were decreased
Semaglutide	0.5-1.0 mg once-weekly SC	165.0-184.0	Peptidases and renal	SUSTAIN-6[67]	Nephropathy > 35% was decreased. Progression to macroalbuminuria was decreased. Doubling of serum creatinine levels was decreased. eGFR of ≤ 45 mL/min per 1.73 m2 was decreased. The initiation of renal replacement therapy decreased
Dulaglutide	0.75-1.5 mg once-weekly SC	About 112.8	Peptidases and renal	AWARD VII[66]	Reduced albuminuria, slower decline in renal function
Albiglutide	30-50 mg once-weekly SC	About 120.0	Peptidases and renal	None	None

GLP-1: Glucagon-like peptide-1; SC: Subcutaneous; UACR: Urinary albumin-to-creatinine ratio; RAS: Renin-angiotensin-system; eGFR: Estimated glomerular filtration rate; LEADER: Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; SUSTAIN-6: Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes 6.