Scientists tested two experimental drugs (pimozide and PSSI-51) that might help control blood sugar in people with type 2 diabetes. They gave these drugs to rats and measured how the animals’ bodies processed them. The interesting discovery: when rats ate a high-fat diet, one drug (pimozide) moved through their bodies differently than when they ate normal food. The other drug (PSSI-51) wasn’t affected by diet changes. This matters because what we eat might change how well diabetes medications work in our bodies, which could be important for people taking these drugs in the future.

The Quick Take

  • What they studied: How two experimental diabetes drugs move through the body and whether eating fatty foods changes how quickly the body processes these drugs
  • Who participated: Male and female Sprague-Dawley rats (a common laboratory rat breed) divided into groups that ate either normal food or high-fat food for 10-13 weeks
  • Key finding: Pimozide was processed differently by rats on a high-fat diet—their bodies cleared it more slowly and distributed it differently. PSSI-51 worked the same way regardless of diet. This suggests diet might affect how well pimozide works as a diabetes medicine.
  • What it means for you: If these findings hold true in humans, people taking pimozide for diabetes might need different doses depending on their diet. However, this is early research in animals, so we can’t apply it to people yet. Always talk to your doctor about how diet affects your medications.

The Research Details

Researchers conducted a two-part experiment with laboratory rats. In the first part, they gave small groups of rats a single dose of either pimozide or PSSI-51 by mouth, then collected blood samples multiple times to measure how much drug was in the blood and how fast the body eliminated it. In the second part, they repeated this experiment with rats that had eaten either normal food or high-fat food for 10-13 weeks to see if diet changed how the body handled these drugs. They used mathematical models to analyze the blood samples and understand the drugs’ movement through the body.

Understanding how drugs move through the body (called pharmacokinetics) is crucial before testing them in humans. If diet changes how a drug works, doctors need to know this to prescribe the right dose. This research helps identify potential problems early, making future human testing safer and more effective.

This is early-stage laboratory research using animals, which is an important first step but doesn’t directly prove how drugs work in humans. The study used small numbers of rats (about 5 per group initially), which is typical for this type of preliminary work. The researchers used established scientific methods and mathematical analysis to interpret their results. However, rat metabolism differs from human metabolism, so results may not directly apply to people.

What the Results Show

The two drugs behaved quite differently in the rats’ bodies. Pimozide followed a simpler one-compartment model (meaning it distributed to one main area of the body), while PSSI-51 followed a two-compartment model (distributing to multiple areas). Both drugs spread widely throughout the body, but PSSI-51 was cleared much faster than pimozide. The high-fat diet had a significant effect on pimozide: rats eating fatty food had slower clearance (the body took longer to eliminate the drug) and smaller volume of distribution (the drug didn’t spread as widely). This suggests that eating fatty foods might cause pimozide to stay in the body longer and concentrate more in certain areas. In contrast, PSSI-51 was unaffected by diet—it moved through the body the same way whether rats ate normal or high-fat food.

The researchers found that both male and female rats responded similarly to the diet changes, suggesting that sex doesn’t significantly influence how these drugs interact with diet. The results confirmed earlier laboratory findings showing that PSSI-51 is cleared from the body much faster than pimozide, which aligns with previous research using rat liver cells.

These findings support earlier research conducted in laboratory settings using rat liver cells, which showed that PSSI-51 is processed much more quickly than pimozide. The new study extends this knowledge by showing how a high-fat diet affects this process in living animals. This is an important step toward understanding real-world conditions where people eat different types of diets.

This study used rats, not humans, so results may not directly apply to people—our bodies process drugs differently. The initial groups were very small (5 rats each), which limits confidence in the findings. The study only tested a single dose of each drug, so we don’t know how repeated doses would be affected by diet. The research doesn’t explain why high-fat diet affects pimozide but not PSSI-51, leaving questions about the underlying mechanism. Finally, this is preliminary research, and much more testing is needed before these drugs could be used in patients.

The Bottom Line

This is very early research that should not influence current medical practice. For people currently taking diabetes medications: continue taking your medications as prescribed and consult your doctor before making any changes. For future patients: if pimozide or PSSI-51 become available as diabetes treatments, your doctor will determine the appropriate dose based on clinical trials in humans. The diet-drug interaction found in rats may or may not occur in people, so human studies are essential. Confidence level: Low—this is animal research only.

Researchers developing new diabetes drugs should pay attention to these findings as they plan human studies. People with type 2 diabetes should be aware that diet can potentially affect how medications work, making this an area for future research. Healthcare providers should note that drug-diet interactions may need to be considered when prescribing new diabetes medications. People currently taking pimozide for other conditions (it’s used for certain psychiatric conditions) should not change their diet or medication based on this rat study.

This is fundamental research, not a treatment ready for use. If these findings are confirmed in human studies, it would likely take 5-10 years before any new diabetes drug based on this research could become available to patients. Even then, the practical impact on dosing would depend on how significant the diet effect is in humans.

Want to Apply This Research?

  • If you’re participating in a diabetes medication study, track your daily fat intake (grams of fat per day) alongside your blood sugar readings to help researchers understand if diet affects your medication’s effectiveness
  • For future users: once these drugs are available, use the app to log your meals and note the fat content, then correlate this with your blood sugar patterns to identify if your diet affects how well your medication works
  • Maintain a 2-week food diary noting fat intake and corresponding blood sugar readings, then review patterns with your healthcare provider to determine if dietary adjustments might improve medication effectiveness

This research was conducted in laboratory rats and does not directly apply to human treatment. Pimozide and PSSI-51 are experimental drugs not yet approved for diabetes treatment in humans. If you have type 2 diabetes, continue following your doctor’s treatment plan and do not make changes based on this animal research. Always consult with your healthcare provider before modifying your diet or medications. This summary is for educational purposes only and should not be considered medical advice.