About Us Medical Scholars Program Curriculum Magazine Enrollment Login

A Combination Approach in the Treatment of Type II Diabetes and Obesity

written by joshuamel sambrano Mar 19, 2024

The prevalence of obesity and type II diabetes continues to rise in the United States. Obesity is a disorder that involves having too much adipose or fat tissue and is medically defined as a body mass index (BMI) of 30 or greater. Type II diabetes, which constitutes the majority of diabetes diagnoses, is characterized by increased amounts of glucose in the bloodstream due to defective insulin secretion, insulin action, or both. Insulin helps regulate the amount of glucose in your blood. If there is too much glucose, insulin is released and helps cells uptake glucose for energy production or storage. In your pancreas, the β-cell is responsible for making insulin. Defects in insulin production and/or function contribute to the onset of diabetes. To know more about Diabetes, see our prior article: Why should I care about Diabetes? 

Patients with obesity are six times more likely to develop diabetes than non-obese patients.  Thus, there has been a lot of research into developing treatments that target both conditions simultaneously.

So, what exactly are some of those combination approaches?

CagriSema  

CagriSema is a dual-combination drug consisting of a drug called cagrilintide and a drug known as semaglutide. You may have heard of semaglutide by its trade name, Ozempic. Semaglutide acts on a receptor (GLP-1) that helps with glucose control and weight loss. Cagrilintide acts as an analog of amylin, which is a hormone that causes a feeling of fullness, which decreases food intake and promotes weight loss. In clinical trials, the co-formulation of these two drugs has shown an average weight loss of 17.1% and an improved blood sugar.

CagriSema works to:

  • Promote weight loss

  • Decrease blood sugar (improve A1C, a measurement of blood sugar over the past 3 months)

Common side effects:

  • Diarrhea

  • Belching

  • Bloating

  • Nausea and vomiting

Tirzepatide

Tirzepatide activates two receptors in your body, GIP and GLP-1. Activation of the GIP receptor results in increased release of insulin from the pancreas and inhibits glucagon, a hormone which typically increases blood sugar. Increased insulin and decreased glucagon result in decreased blood sugar. Activation of the GLP-1 receptor results in slowed emptying of the stomach, causing feelings of fullness and decreased appetite, which leads to decreased food intake and weight loss. This is the same mechanism as was discussed above in the common medication Ozempic. By acting on two different receptors, Tirzepatide has an increased effect towards weight loss. In clinical trials, this drug resulted in a reduction in 3 month blood sugar levels (A1c) by 2 percent and a weight reduction of about 12-23 pounds depending on dose.

Tirzepatide works to:

  • Promote weight loss

  • Decrease blood sugar (improved A1C) 

Common side effects:

  • Stomach pain/discomfort

  • Belching

  • Constipation

  • Diarrhea

Retatrutide 

Retatrutide is a triple-combination or “triagonist” medication. It acts on three hormones: GIP, GLP-1, and the glucagon receptor. We already discussed the GIP and GLP-1 receptors above. The added effect of acting on the glucagon receptor in Retatrutide allows for further reducing appetite and burning more energy. Retatrutide, still early in its clinical trial phases, has shown promising results. In a phase 2 study with 338 adults with obesity who received 48 weeks of treatment, there was an astonishing 24% or 55 pounds of weight loss on average. A different study involving patients with type 2 diabetes showed almost 17% average weight loss, improved blood sugar levels, decreased “bad” cholesterol (LDL), and improved blood pressure. 

Retatrutide works to:

  • Promote weight loss

  • Decrease blood sugar (improved A1C) 

  • Decrease LDL 

  • Improve blood pressure 

Common side effects:

  • Nausea

  • Diarrhea

  • Vomiting

  • Constipation

Diabetes treatment options are continuing to be tested, observed, and improved today through clinical research. While there are many options for weight loss treatment, whether by oral medication or injectables like the mentioned drugs above, there is still a shortage in the availability of these medications all over the U.S. However, knowledge of these new combination approaches allows those seeking treatment to be informed about what route they should take. If you or someone you know is looking for treatment for type II diabetes or obesity, consult with your provider about the best available options for you. 

 

Written by JoshuaMel Sambrano

Edited by Ali Aljassabi & Mallory Kane

 

References

  1. Chavda, Vivek P et al. ``Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review.” Molecules (Basel, Switzerland) vol. 27,13 4315. 5 July. 2022, doi:10.3390/molecules27134315

  2. Chong, Keong, et al. “Recent Advances in the Treatment of Type 2 Diabetes Mellitus Using New Drug Therapies.” Wiley Online Library, 12 Dec. 2023, onlinelibrary.wiley.com/doi/10.1002/kjm2.12800. 

  3. European Association for the Study of Obesity. “New Experimental Drug Cagrilintide (AM833), When Combined with Semaglutide, Shows Potential for Treatment of Obesity.” Medical Xpress - Medical Research Advances and Health News, Medical Xpress, 13 May 2021, medicalxpress.com/news/2021-05-experimental-drug-cagrilintide-am833-combined.html. 

  4. Jastreboff, Ania M., and Robert F. Kushner. “New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics.” Annual Reviews of Medicine, Jan. 2023, www.annualreviews.org/doi/abs/10.1146/annurev-med-043021-014919. 

  5. Leclercq, I.A., et al. “Hepatic Insulin Resistance, Metabolic Syndrome and Cardiovascular Disease.” Clinical Biochemistry, Elsevier, 9 June 2009, www.sciencedirect.com/science/article/abs/pii/S0009912009002513. 

  6. Milstein, Joshua L, and Heather A Ferris. “The brain as an insulin-sensitive metabolic organ.” Molecular metabolism vol. 52 (2021): 101234. doi:10.1016/j.molmet.2021.101234

  7. Padhi, Santwana & Nayak, Amit & Behera, Anindita. (2020). Type II diabetes mellitus: a review on recent drug based therapeutics. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 131. 110708. 10.1016/j.biopha.2020.110708. 

  8. Pettway, Yasminye D et al. “The human α cell in health and disease.” The Journal of endocrinology vol. 258,1 e220298. 19 June. 2023, doi:10.1530/JOE-22-0298

  9. Plum, Leona et al. “The role of insulin receptor signaling in the brain.” Trends in endocrinology and metabolism: TEM vol. 16,2 (2005): 59-65. doi:10.1016/j.tem.2005.01.008

  10. Ralph A. DeFronzo; From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus. Diabetes 1 April 2009; 58 (4): 773–795. https://doi.org/10.2337/db09-9028

  11. Verma, Narsingh. “Ominous Octet Diabetes.” My Endo Consult, 7 June 2023, myendoconsult.com/learn/the-ominous-octet-of-t2dm-m-o-a/?print=print#t-1707176282254.