"Twincretin": A New Class of Diabetes Medication

A Healthier You

"Twincretin": A New Class of Diabetes Medication

Staci NormanContributor: Dr. Staci-Marie Norman, PharmD, DCES

Spring can be a time for new beginnings, so let's talk about a relatively new medication in the diabetes arsenal, starting with the basics of this new drug class and drug.

Tirzepatide (Mounjaro™) was approved by the FDA in May 2022 and hit the market in September 2022. It's the only medication in a new class called GLP-1 Receptor Agonist/GIP combination (or "twincretin" based on GLP-1 and GIP both being incretin hormones produced in the intestinal system).

  • GLP-1 is a hormone naturally produced in the intestines when food is present. It helps signal the pancreas to produce insulin to bring down post-meal blood glucose while signaling the liver to stop producing sugar because the body is not fasting. GLP-1 also helps slow food transition through the stomach and acts as a neurotransmitter to the satiety center in the brain, stimulating the feeling of fullness when eating. GLP-1 RA medications include Byetta, Bydureon, Ozempic, Victoza, and Trulicity.
  • GIP has many of the same functions as GLP-1 but does not act as a neurotransmitter in the brain. However, GIP does have some action within adipose (fat) tissue that GLP-1 does not have. The exact way GIP acts within adipose tissue hasn't been fully figured out, but it is thought that it helps sensitize the adipose tissue to insulin, a function often lacking in those with type 2 diabetes.

Combining GLP1 and GIP has led to incredible clinical trial results in blood glucose management and weight loss. There were a series of clinical trials where Mounjaro was compared against placebo (diet and exercise), Ozempic, Lantus, and Tresiba.  Mounjaro outperformed the placebo or other medications in each of these trials by a statistically significant margin. Participant's A1C was lowered between 1.9% and 2.6% depending on the dose of Mounjaro. This represents a larger A1C reduction than other non-insulin medications. Approximately 82-93% of the clinical trial participants reached the ADA goal of A1C <7%.

The clinical trials also showed significant weight reduction associated with Mounjaro use. Participants lost anywhere from 1.9kg to 15.2kg more than the drug it was being studied against. That’s approximately 5 to 30 pounds difference. This potential for weight loss is part of the frenzy around Mounjaro. Currently, there is no FDA approval for Mounjaro to be used for weight loss alone, but due to its ability to produce fairly significant weight changes, it has been used by physicians who treat obesity. An ongoing clinical trial is currently looking at weight loss in people without diabetes. Those results are expected sometime in 2024.

Here are some tips for the successful use of this new drug:

  1. It is titrated from a tiny dose once weekly to the clinically effective amount for you. The typical starting dose is 2.5mg weekly for a month, increased by 2.5mg weekly at monthly intervals. The clinically effective doses in clinical trials ranged from 10 to 15mg.
  2. Major side effects of this medication are nausea, vomiting, and diarrhea. This is all due to the effect on the stomach as the transition of food is slowed. It is part of the reason for starting with a very low dose and giving your body time to adjust. You can also help limit these side effects by eating smaller portions, avoiding fatty foods, and eating slowly, allowing your body to feel full without overeating.
  3. If you start to have intolerable side effects as you increase your dose,  you can always talk to your doctor about stepping back down to give your body more time to adjust before increasing the dose again.
  4. For those using oral birth control for pregnancy prevention, it is imperative to use barrier contraception (condoms) for a month when starting and for a month with each dose increase. It is thought that there may be some absorption changes to the oral contraceptive due to the change in stomach motility, leading to less efficacy. Once at a stable dose, this absorption problem is thought to resolve.

Those prescribed Mounjaro in the past few months may have had trouble finding it. The demand has been greater than expected, and scaling up production has yet to be able to keep up, leading to many doses being back ordered or limited. This is expected to be rectified soon.

Dr. Staci-Marie Norman, PharmD, DCES, received her bachelors from Purdue University (’94) and her Doctor of Pharmacy from the University of Oklahoma (’96). In 2000 Dr. Norman added to her credentials by becoming a Certified Diabetes Care and Education Specialist. She is currently the Clinical Coordinator and staff pharmacist for Martin’s Pharmacy. Dr. Norman is a national faculty member for the American Pharmacist Association, teaching certificate programs in both diabetes and cardiovascular disease. She serves on the advisory board that oversees development and revision of these programs. Along with teaching and development responsibilities for APhA, Dr. Norman serves as a peer reviewer for research grants and publication submission. Dr. Norman has also spoken for Abbott, Bayer, Lilly, Mannkind, and Lifescan as a diabetes specialist.