Short answer: Actos (pioglitazone) and Januvia (sitagliptin) are once-daily tablets for blood sugar in adults with type 2 diabetes, from different drug classes.12 Actos has a boxed warning that it can cause or worsen heart failure, and swelling and weight gain rise with its dose. Januvia has no boxed warning and its dose is lowered for weak kidneys. Neither label reports a trial against the other.
| Actos (pioglitazone) | Januvia (sitagliptin) | |
|---|---|---|
| Drug class | Thiazolidinedione1 | DPP-4 inhibitor2 |
| Dose | 15 or 30 mg once a day, up in 15 mg steps to 45 mg1 | 100 mg once a day, no step-up2 |
| Dose limits | 15 mg with gemfibrozil; 15 mg start with mild heart failure1 | 50 mg at eGFR 30 to under 45; 25 mg under 30 or on dialysis2 |
| Boxed warning | Can cause or worsen congestive heart failure1 | None2 |
| Weight (on its own) | Median +0.9 to +2.6 kg on 15 to 45 mg vs −1.4 kg on placebo1 | Not listed as a side effect2 |
| Swelling (on its own) | 2.5% to 6.5% by dose vs 1.2%1 | Not in the monotherapy table2 |
| Most common side effects | Upper respiratory infection 13.2% vs 8.5%; headache 9.1% vs 6.9%1 | Stuffy or runny nose with sore throat 5.2% vs 3.3%2 |
| Other warnings | Fractures in women, bladder cancer, macular edema, liver effects1 | Pancreatitis, kidney failure, severe joint pain, bullous pemphigoid, heart failure2 |
Actos helps the body use its own insulin better, which is why the label says it works only when the body still makes insulin.1 Januvia blocks the DPP-4 enzyme, which raises gut hormones that help release insulin after meals.2 The Januvia label includes a 24-week trial of Januvia added to pioglitazone.2
The Actos label says thiazolidinediones cause or worsen heart failure in some people, and starting it is contraindicated in NYHA Class III or IV heart failure. In the PROactive trial, hospitalized heart failure was 5.7% vs 4.1% on placebo, and swelling 27.3% vs 15.9%. Weight went up a median 3.6 kg vs down 0.5 kg.1 Fractures in women were 5.1% vs 2.5%.1
The Januvia label also lists heart failure among its warnings, but without a boxed warning.2 These numbers come from separate trials with different people, lengths and methods, so they are not a head-to-head comparison.
Your prescriber weighs heart, kidney and bone health in choosing. More detail: Actos side effects, Januvia side effects, the Actos and Januvia dosing schedules, and the Pioglitazone and Sitagliptin guides.