Trulance (plecanatide) does not cause weight gain. Weight gain was not reported as a side effect in any of the clinical trials for the drug, and it does not appear in the FDA-approved prescribing information as an adverse reaction. The only side effect that occurred in more than 2% of patients was diarrhea. If you’ve noticed weight changes while taking Trulance, something else is likely going on.
How Trulance Works in the Body
Trulance mimics a natural hormone called uroguanylin that activates receptors along the lining of your intestines. When these receptors are triggered, your intestinal cells release chloride, bicarbonate, and water into the gut. This extra fluid softens stool and makes bowel movements easier, which is why the drug is prescribed for chronic constipation and irritable bowel syndrome with constipation (IBS-C).
One important detail: Trulance is not absorbed into your bloodstream. After you take a 3 mg dose, the drug and its active byproduct remain at levels too low to even measure in plasma. It works entirely within the intestinal tract. This means it has no direct pathway to affect your metabolism, fat storage, appetite hormones, or any other system that would lead to weight gain.
What the Research Says About Metabolism
Researchers have specifically looked at whether the type of receptor Trulance targets (called GC-C) plays any role in energy balance or blood sugar regulation. In animal studies, mice that completely lacked the GC-C receptor had normal body weight, normal fat levels, and normal glucose tolerance. When researchers administered GC-C-activating compounds directly into the central nervous system, there was no significant change in food intake.
There was one interesting finding: mice missing uroguanylin (the natural hormone Trulance mimics) showed a small increase in body weight and fat. If anything, this suggests that having more GC-C activity, not less, would lean toward weight neutrality or even modest metabolic benefit. But the effects were small, and the researchers concluded they weren’t driven by the same receptors Trulance activates in the gut.
Why You Might Feel Heavier on Trulance
Even though Trulance itself doesn’t cause weight gain, a few things can create that impression. The drug increases fluid secretion into your intestines. In some people, this shift in fluid distribution can cause temporary bloating or a feeling of fullness, especially in the first days or weeks of treatment. That sensation can feel like weight gain even when your actual body composition hasn’t changed.
It’s also worth considering what was happening before you started the medication. Chronic constipation itself causes bloating, abdominal distension, and fluctuations on the scale depending on how backed up your system is. As your bowel patterns change with treatment, your day-to-day weight can swing by a few pounds simply based on stool and water content. These shifts are temporary and don’t reflect fat gain.
Other Possible Explanations
If you’re genuinely gaining weight while taking Trulance, it’s worth looking at other factors that coincided with starting the medication. Many people with IBS-C make dietary changes alongside treatment, sometimes eating more because reduced constipation makes meals more comfortable. Certain foods recommended for gut health, like higher-fiber options with added fats or calorie-dense smoothies, can contribute to gradual weight gain that gets attributed to the pill rather than the plate.
Other medications taken at the same time are another common culprit. If you started or changed a different prescription around the same period you began Trulance, that drug may be the actual cause. Medications for mood disorders, hormone therapy, and certain blood pressure drugs are well-known contributors to weight gain and are frequently taken alongside GI treatments.
Hormonal changes, stress, reduced physical activity due to GI discomfort, and normal aging-related metabolic shifts can all overlap with the start of a new medication and create a false association. Tracking your calorie intake and activity level for a few weeks can help clarify whether something beyond Trulance is driving the change.
What Trulance Side Effects Actually Look Like
The side effect profile for Trulance is relatively narrow. In combined clinical trials for chronic constipation, 5% of patients on Trulance experienced diarrhea compared to 1% on placebo. In IBS-C trials, the diarrhea rate was 4.3% versus 1% on placebo. That was the only adverse reaction that exceeded the 2% threshold. Gas, abdominal discomfort, and nausea have been reported but at low rates.
If anything, patients are more likely to lose a small amount of weight on Trulance than gain it. Relieving constipation reduces the physical buildup of stool and associated water retention in the gut, which can show up as a modest drop on the scale in the first weeks of treatment.