GLP-1 Receptor Agonists and Risk of Kidney Replacement Therapy and Health Care Utilization in Bipolar Disorder With Chronic Kidney Disease
- Design
- Retrospective cohort · 7816 participants · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationINDIRECT: adults with bipolar disorder and chronic kidney disease (stage ≤3), a kidney disease the target group does not have; BMI, age and diabetes status are not reported in the abstract.
- Could weight loss explain it?
- PossiblyPossibly: the abstract reports no weight, HbA1c or mediation analysis; propensity matching balances baseline traits but does not separate a drug effect from weight or glycaemic change, and the obesity subgroup tests effect modification, not mediation.
- Study tier
- Study tier 3LOW: a single retrospective database cohort with propensity matching; the observational design caps it at LOW.
- Assessment
- Version 3 · Two reviewers differed; settled by a recorded ruling · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
This retrospective database study compared adults with bipolar disorder and chronic kidney disease who started a GLP-1 drug with matched people starting a DPP-4 inhibitor (3,908 per group) over 5 years. GLP-1 drug use was linked to a lower risk of needing kidney replacement therapy (aHR 0.56), but survival free of health care use did not differ after matching. Because it is observational, it shows an association, not that the drugs caused the difference.
01Findings
What the study reported
- Drugs
- Glp-1 receptor agonists
- Comparator
- DPP-4 inhibitors (primary); renin-angiotensin-aldosterone system (RAAS) inhibitors (secondary)
- Dose
- various
- Primary outcome
- kidney replacement therapy (KRT) and health care utilization (HCU)
- Effect
- Versus DPP-4 inhibitors: KRT aHR 0.56 and HCU aHR 0.74; after PSM, 5-year KRT-free survival 87.93% vs 84.63% but HCU-free survival did not differ (P=.89). Versus RAAS inhibitors: KRT aHR 0.66 and HCU aHR 0.62; after PSM, KRT-free survival 94.68% vs 89.77% but HCU-free survival did not differ (P=.15)
- 95% confidence interval
- KRT aHR 0.56, 95% CI 0.50-0.64; HCU aHR 0.74, 95% CI 0.71-0.78
- P value
- KRT-free survival P<.001; HCU-free survival P=.89 (versus DPP-4 inhibitors after matching)
- Follow-up
- 5-year follow-up
- Adverse events
- not reported in abstract
- Limitations
- A retrospective database cohort with propensity matching, so residual confounding remains; the authors call the findings exploratory and say prospective studies are needed to test whether the association is causal.
Who was studied
- Obesity status
- mixed (obesity examined as a subgroup)
- Diabetes status
- not reported in abstract
- Cvd status
- not reported in abstract
- Ckd status
- chronic kidney disease (stage ≤3) required
- Baseline condition
- bipolar disorder with chronic kidney disease (stage ≤3)
- Sample size
- 7816
- Inclusion exclusion
- adults with bipolar disorder and CKD stage ≤3 who were new users of a GLP-1 RA, DPP-4 inhibitor or RAAS inhibitor
Study quality details
- Study design
- Retrospective cohort
- Sample size
- 7816
- Randomization
- no
- Blinding
- n/a
- Comparator
- DPP-4 inhibitors (primary); renin-angiotensin-aldosterone system (RAAS) inhibitors (secondary)
- Follow up duration
- 5-year follow-up
- Outcome type
- hard
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- INDIRECT
- Statistical precision
- aHRs with 95% CIs for the DPP-4 comparison; 3,908 per group after matching; no event counts reported
- Risk of bias
- not assessed
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- One author reports academic, foundation and NIH grant support and editing honoraria from Elsevier, another advisory work for Alexion and site-investigator work for AstraZeneca, and another foundation grant funding and research funding from Supernus; one reports none.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
Objective: To examine whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) use is associated with reduced risk of kidney replacement therapy (KRT) and health care utilization (HCU) compared with active comparators in adults with bipolar disorder (BD) and chronic kidney disease (CKD; stage ≤3). Methods: Using TriNetX, we conducted a real-world, new-user active-comparator cohort study among adults with BD+CKD initiating GLP-1 RA or dipeptidyl peptidase-4 (DPP-4) inhibitor therapy (primary comparator), with a secondary analysis versus renin-angiotensin-aldosterone system (RAAS) inhibitor users. Propensity score matching (PSM) balanced baseline characteristics. Cox proportional hazards regression estimated adjusted hazard ratios (aHR) for KRT and HCU over 5-year follow-up. Subgroup analyses examined effect modification by sex, race, ethnicity, obesity, and psychotropic medication use. Results: Compared with DPP-4 inhibitor use, GLP-1 RA use was associated with lower observed risk of KRT (aHR 0.56, 95% CI 0.50-0.64) and HCU (aHR 0.74, 95% CI 0.71-0.78). Following PSM (n=3,908 per group), 5-year KRT-free survival was 87.93% versus 84.63% (P<.001); HCU-free survival did not differ significantly (P=.89). Versus RAAS inhibitors, GLP-1 RA use was similarly associated with lower observed risk of KRT (aHR 0.66) and HCU (aHR 0.62); after PSM (n=2,539 per group), KRT-free survival was higher (94.68% vs. 89.77%; P<.001), while HCU-free survival did not differ significantly (P=.15). Benefits were consistent across sex, race, and obesity status and across psychotropic subgroups, including lithium. Conclusions: GLP-1 RA use was associated with lower observed risk of KRT and HCU compared with DPP-4 inhibitors, corroborated for KRT in a secondary comparison against RAAS inhibitors. These exploratory findings warrant further investigation, including prospective studies, to evaluate whether this association reflects a causal effect.