Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide

People with mild, moderate or severe renal or hepatic impairment had largely similar cagrilintide exposure to people with normal organ function after a single subcutaneous dose, with AUC ratios close to 1.0 in both studies. The drug was well tolerated, with no serious adverse events, withdrawals or deaths. The authors conclude that no dose adjustment is needed for renal or hepatic impairment, within the limits of the small sample sizes.

Randomized controlled trial — Two phase I multicentre studies. Population: Adults with normal renal or hepatic function or mild, moderate or severe renal or hepatic impairment. Sample size: 33 participants (renal study); 32 participants (hepatic study). Follow-up: Day 1 to day 36 (renal study); day 1 to day 39 (hepatic study). Interventions: Cagrilintide 0.6 mg single subcutaneous dose (renal impairment study); Cagrilintide 0.9 mg single subcutaneous dose (hepatic impairment study).

In the renal impairment study (33 participants), the estimated ratios of mean AUC 0-∞ versus normal function were 1.23 (90% CI 0.91-1.66) for mild, 1.18 (0.87-1.59) for moderate and 1.21 (0.87-1.68) for severe impairment. In the hepatic impairment study (32 participants), the corresponding ratios were 0.99 (0.89-1.11) for mild, 1.01 (0.91-1.12) for moderate and 1.11 (0.96-1.30) for severe impairment. Total exposure, Cmax and other pharmacokinetic parameters were similar across groups, with no consistent pattern observed with renal or hepatic impairment. Treatment-emergent adverse events were reported in 11 participants (21 events) in the renal study and 9 participants (16 events) in the hepatic study, with no serious events, study withdrawals or deaths, and no increase in events with worsening organ function. The authors concluded that no clinically relevant pharmacokinetic differences were seen and no dose adjustment is warranted.

These are the dedicated renal and hepatic impairment pharmacokinetic studies for cagrilintide, and they directly inform whether dose adjustment is warranted in these populations. The data do not establish the effects of repeated dosing, the CagriSema fixed-dose combination itself, or any efficacy outcomes, and the small severe-impairment groups limit precision. Researchers building the cagrilintide evidence base will use these single-dose exposure and tolerability data to support dosing decisions.

Key findings

• Total cagrilintide exposure (AUC 0-∞) ratios versus normal renal function were 1.23 (mild), 1.18 (moderate) and 1.21 (severe) impairment.
• Total cagrilintide exposure (AUC 0-∞) ratios versus normal hepatic function were 0.99 (mild), 1.01 (moderate) and 1.11 (severe) impairment.
• Cmax, tmax and other pharmacokinetic parameters were similar across all renal and hepatic function groups, with no consistent pattern by severity.
• 21 treatment-emergent adverse events occurred in 11 of 33 participants in the renal study; 16 occurred in 9 of 32 in the hepatic study.
• No serious adverse events, study withdrawals or deaths were reported in either study.
• The authors concluded that cagrilintide dose adjustment is not warranted for renal or hepatic impairment.

Limitations

• Small sample sizes, particularly in the severe impairment groups (n = 5 in the renal study; n = 4 in the hepatic study).
• Only single doses of cagrilintide were studied, so repeated-dose pharmacokinetics and safety in impaired populations were not assessed.
• 90% confidence intervals around the AUC ratios were wide (e.g., 0.87-1.68 for severe renal impairment), limiting precision.
• The studies were phase I pharmacokinetic trials, not designed to evaluate efficacy or rare adverse outcomes.

The record

• Journal: Clinical pharmacokinetics 65(7): 1087-1099
• Published: 2026-06-01
• PMID: 42228334 — DOI: 10.1007/s40262-026-01654-0
• MeSH terms: Humans, Liver Diseases, Hypoglycemic Agents, Injections, Subcutaneous, Area Under Curve, Adult, Aged, Middle Aged, Female, Male, Renal Insufficiency, Glucagon-Like Peptides, Semaglutide
• Author countries: Denmark, Slovakia, Switzerland

Peptide profiles: Cagrilintide.

All indexed evidence: Cagrilintide trials & papers.

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