Short answer: It is done, and the Actos label gives trial data for it, but it flags two risks. Fluid retention is most common when pioglitazone is used with insulin and can lead to or worsen heart failure, and low blood sugar becomes more likely. In a 16-week trial, swelling occurred in 17.6% on Actos 30 mg with insulin versus 7.0% on insulin alone. If lows happen, the label says to cut the insulin dose by 10% to 25%.
Actos (pioglitazone) is a thiazolidinedione. Its boxed warning says drugs in this class cause or worsen heart failure in some people. It asks for careful watching for signs after starting and after each dose increase: fast or excessive weight gain, shortness of breath and swelling. Actos is not recommended with symptomatic heart failure, and starting it is contraindicated (not to be used) with NYHA class III or IV heart failure.
Section 5.1 says the fluid retention is dose-related and most common with insulin. Insulin labels carry the matching warning: the Lantus label says patients on insulin and a PPAR-gamma agonist such as pioglitazone are watched for heart failure, and that stopping or lowering the pioglitazone is considered if it develops (section 5.7).
| Reaction | Placebo + insulin (187) | Actos 15 mg + insulin (191) | Actos 30 mg + insulin (188) |
|---|---|---|---|
| Low blood sugar | 4.8% | 7.9% | 15.4% |
| Swelling (edema) | 7.0% | 12.6% | 17.6% |
| Weight increased | 0.5% | 5.2% | 6.4% |
| Heart failure event | 0 | 1.0% | 1.1% |
A 24-week trial without a placebo group compared two Actos doses added to insulin. On 30 mg vs 45 mg, low blood sugar was reported in 43.5% vs 47.8%, swelling in 22.0% vs 26.1%, weight gain in 7.2% vs 13.9%, and heart failure events in 0.9% vs 1.4% (Tables 4 and 6). None of the heart failure events in these trials were fatal.
Pioglitazone makes the body more sensitive to insulin, so the same insulin dose can lower blood sugar further. The label says that if low blood sugar happens on Actos with insulin, the insulin dose is decreased by 10% to 25%, with further changes based on glucose readings (section 2.2). For a sulfonylurea, it says that dose is reduced instead.
The NIDDK treats a reading under 70 mg/dL as low for many people and describes the 15-gram rule for treating it. See what happens if you take too much insulin for more on lows.
Because the label's heart failure signs include rapid weight gain, a daily or weekly weight log is useful on this pair. Swollen ankles, getting short of breath on less effort and needing extra pillows to sleep are worth a call to the prescriber. See does insulin cause weight gain for how weight changes on insulin alone.
Dose Track keeps insulin doses, weight and glucose notes on one timeline, which shows whether a weight jump lines up with starting or raising pioglitazone.
Read more on Dose Track: Actos side effects · Actos dosing schedule · Thiazolidinedione · Pioglitazone vs metformin