Table 1 Key features of antidiabetic drugs and relevant effects on depression.
From: The interface of depression and diabetes: treatment considerations
Pharmacological class (drug) | Place in therapy for T2DM | Effect on body weight | Most common side effects | Rare but life-threatening side effects | Clinical evidence on depression/depressive symptoms | Other notes | Potential PK interactions with antidepressants (bidiretional) |
|---|---|---|---|---|---|---|---|
Biguanide (metformin) | First-line agent | Neutral effect (changes in gut microbiome) | Gastrointestinal complaints (nausea, diarrhea), vitamin B12 deficiency | Lactic acidosis (if multiple risk factors) | Inconsistent data | Recommended to treat antipsychotic-induced diabetes (psychotic depression) | Unlikely PK interactions (except in case of renal impairment) |
SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin) | Second-line agents (preferentially in HF, CKD) | Slight reduction (diuretic and natriuretic effect), including fat mass | UTIs, GTIs, hypovolemia/dehydration | DKA, amputation (debated association, especially for canagliflozin), FG | Very limited but encouraging data from observational studies | Useful to reduce the cardiovascular risk/burden in case of comorbidities (e.g., HF), or counteract hyponatremia by SSRIs | Unlikely PK interactions |
GLP-1 receptor agonists (e.g., semaglutide, liraglutide) | Second-line agents (preferentially in ASCVD) | Substantial reduction (appetite suppression and increased gastric emptying), including lean mass | Gastrointestinal complaints (nausea, vomiting, diarrhea) | Intestinal obstruction, gallbladder, biliary disorders, pancreatitis, thyroid cancer (debated long-term association), diabetic retinopathy (debated association) | Unclear relationship: potential benefit from a few cohort studies, and under regulatory investigation for post-marketing reports of suicidality (debated association) | Useful to reduce the cardiovascular risk/burden and counteract antidepressant-induced weight gain | Unlikely PK interactions |
DPP-4 inhibitors (e.g., sitagliptin, linagliptin) | Second-line agents | Neutral/slight reduction (appetite inhibition) | Gastrointestinal complaints (nausea, vomiting, diarrhea) | Intestinal obstruction, gallbladder/biliary disorders, pancreatitis, arthritis/arthralgia, bullous pemphigoid | No data | Unclear cardiovascular benefit (to be avoided in HF) | Low potential for PK interactions |
Glitazones (pioglitazone) | Second-line agents | Increased (fluid retention) | Hypertension and HF | Bladder cancer (long term), macular edema, fractures | Some promising data, but unclear clinically relevant benefit collectively | Unclear cardiovascular benefit (to be avoided in HF) | Low potential for PK interactions |
