# Depression Risk on GLP-1 Drugs vs DPP-4 and SGLT2 Inhibitors | This GLP A Medicare target trial emulation found a depression hazard ratio of 0.90 for GLP-1 against DPP-4 inhibitors and 1.07 against SGLT2 inhibitors. Publisher: This GLP Editorial Team Canonical: https://thisglp.com/research/glp1-depression-depends-on-comparator Updated: 2026-09-18 Published: 2026-09-16 [← Research](https://thisglp.com/research) Evidence # Depression Risk on GLP-1 Drugs vs DPP-4 and SGLT2 Inhibitors In Medicare adults aged 66 and over with type 2 diabetes, the depression hazard ratio was 0.90 against DPP-4 inhibitors and 1.07 against SGLT2 inhibitors. Which one gets quoted depends on the comparator. [This GLP Editorial Team](https://thisglp.com/about)September 20265 min readUpdated September 2026 Risk of depression, against each comparator · 1.0 · vs DPP-4 · 0.82 · 0.98 · vs SGLT2 · 0.98 · 1.18 · Same data, same method, same paper. **Research, not medical advice.** This GLP is independent and educational. Nothing here is a substitute for individualized care from a licensed clinician, and reading it creates no doctor–patient relationship. Talk to your own provider before starting, stopping, or changing any medication, peptide, or therapy. See our [methodology](https://thisglp.com/methodology) and [terms](https://thisglp.com/terms). Whether these drugs move mood in either direction has been argued over for two years, and most of the argument is conducted without naming a comparator. A target trial emulation in US Medicare data makes the point unavoidable: it asked the same question twice, against two different drug classes, and got two different answers [\[1\]](https://thisglp.com/research/glp1-depression-depends-on-comparator#ref-1). It is a useful corrective to the way this claim usually reaches [a seller’s page](https://thisglp.com/best). ## Two comparisons, two answers Adults aged 66 and over with type 2 diabetes were matched on propensity score. Against DPP-4 inhibitors, across 13,711 matched pairs, the rate difference was −5.78 cases of depression per 1,000 person-years (95% CI −10.49 to −1.07), a hazard ratio of 0.90 (95% CI 0.82 to 0.98). That interval clears 1. Against SGLT2 inhibitors, across 14,665 pairs, the rate difference was 3.48 per 1,000 person-years (95% CI −0.81 to 7.78), a hazard ratio of 1.07 (95% CI 0.98 to 1.18). That interval spans 1. So the honest sentence is that GLP-1 use carried a modestly lower depression risk than one comparator and no detectable difference against another. ## Why the comparator is the finding A drug is never tested against nothing in this kind of study. Everyone in both arms was being treated. So a hazard ratio here describes a choice between two treatments, not the effect of taking one. Reading 0.90 as “GLP-1 drugs protect against depression” drops the clause that carries the meaning — the same omission we found where [gout was compared across classes](https://thisglp.com/research/do-glp1-drugs-cause-gout) and where a kidney-stone comparison [ran the other way](https://thisglp.com/research/do-glp1-drugs-cause-kidney-stones). ## The authors rule this market out themselves The stated limitations include unmeasured confounders such as HbA1c and body mass index, and limited generalizability to younger people and to those taking the drug for obesity rather than diabetes. That second clause is this market, named by the paper as out of scope. Everyone studied was 66 or older with type 2 diabetes. Which leaves the same practical point as the rest of the mood evidence, including the [suicidality signal](https://thisglp.com/research/glp1-and-suicidal-ideation): what matters is whether the service you are paying can be reached by someone qualified if your mood changes. That is a question about the seller, and most of them do not answer it — a gap counted in [questions they leave open](https://thisglp.com/tools/questions-they-leave-open). ## Frequently asked Do GLP-1 drugs lower depression risk? Against DPP-4 inhibitors the hazard ratio was 0.90 (95% CI 0.82 to 0.98). Against SGLT2 inhibitors it was 1.07 (95% CI 0.98 to 1.18), which includes no difference. The answer depends on the comparator. Does this apply to someone taking it for weight loss? The authors say not. Their stated limitations include limited generalizability to younger people and to those without type 2 diabetes taking the drug for obesity. How common was depression in the study? The authors describe the incidence as relatively low. The absolute differences were 5.78 fewer cases per 1,000 person-years against DPP-4 inhibitors, and 3.48 more against SGLT2 inhibitors. ## Sources 1. \[1\] Tang H, et al. (2025). Glucagon-Like Peptide-1 Receptor Agonists and Risk for Depression in Older Adults With Type 2 Diabetes : A Target Trial Emulation Study Annals of Internal Medicine. [PMID 39993315](https://pubmed.ncbi.nlm.nih.gov/39993315/) ## Where to get it ### Best GLP-1 injections Every injectable seller we can verify, with the price each one publishes and an honest read of what the trials measured. [Compare providers →](https://thisglp.com/best/compounded-semaglutide) ## More in Evidence - [ 150 minutes · Weekly activity goal · 2 days · Muscle strengthening · Adapt · Symptoms and ability ### Exercise on Ozempic: Building Strength Without Ignoring Symptoms ](https://thisglp.com/research/exercise-on-ozempic) - [ STEP 1, semaglutide 2.4 mg vs placebo, % change at 68 weeks · LDL cholesterol · −2.5% vs +1.3% · Total cholesterol · −3.3% vs +0.1% · HDL cholesterol · +5.2% vs +1.4% · Triglycerides · −21.9% vs −7.3% · Wegovy label, Table 13. Adults without diabetes. Ozempic doses are lower. ### Does Ozempic Lower Cholesterol? What the Lipid Results in the Trials Show ](https://thisglp.com/research/does-ozempic-lower-cholesterol) - [ Where the insulin reduction came from, units per day · week 4 · 13.4 total · week 26 · 21.9 · the drug itself · the weight loss · The drug’s own contribution barely moved: 11.1 then 11.4. · Everything added between weeks 4 and 26 came from weight. ### Does Semaglutide Help Type 1 Diabetes? What Two Small Trials Found ](https://thisglp.com/research/semaglutide-in-type-1-diabetes)