What Do Blue Belgian Cattle Have to Do With Diabetes Management ?
And Why Should Cardiologists Should be Weight Loss Experts ?
Muscle Hypertrophy in Blue Belgium Cattle - Reproduced From Shutterstock by Subscription
Most cardiologists, especially preventive cardiologists, are lipid experts. But cardiologists should also be obesity experts because obesity increases the prevalence of cardiac risk factors such as diabetes and hypertension, and increases the frequency of many cardiac conditions, such as atrial fibrillation.
The Journal of the American Medical Association (JAMA) publishes excellent short summaries of clinical topics. JAMA recently published a summary of new obesity treatments, focusing on the incretin agonists. (1) Here is a brief summary of JAMA’s brief summary.
Incretins are so named because of the observation that oral glucose produced greater increases in insulin levels than intravenously administered glucose.
Glucagon-like peptide-1 (GLP-1) is an incretin secreted by enteroendocrine L-cells in the distal small intestine and colon, and by a small cluster of neurons in the brainstem. GLP-1s slow gastric emptying and reduce glucagon secretion. Glucagon increases glycogenolysis and is used clinically to treat hypoglycemia, so reducing glucagon secretion reduces blood glucose. GLP-1s also reduce appetite by activating brain, vagal nerve and pancreatic receptors.
Glucose-dependent insulinotropic polypeptide (GIP) is another incretin that is produced by enteroendocrine K-cells in the upper small intestine. In contrast to GLP-1s, GIPs do not reduce gastric motility and they stimulate glucagon secretion when there is hypoglycemia. Combining a GIP with a GLP-1 may mitigate the gastrointestinal and metabolic side-effects produced by the GLP-1 alone.
Endogenous GLP-1 and GIP both have short half-lives of 2-4 and 7-10 minutes, respectively, so the drugs that mimic their physiological actions have been modified to be clinically useful.
Semiglutide is a GLP-1 receptor agonist (RA) that can be administered orally as Rybelsus or by injection weekly as Ozempic or Wegovy. Both Rybelsus and Ozempic are approved for patients with type 2 diabetes who are at risk for CV disease. Wegovy is approved for patients with cardiovascular disease who are obese. It is also approved for treatment of nonalcoholic steatohepatitis.
Tirzepatide is a combined GLP-1RA and GIP-1RA and is sold as Monjauro and as Zepbound. Monjauro is approved for treatment of Type 2 diabetes. Zepbound is approved to reduce body weight , obesity and overweight with a weight-related condition including sleep apnea.
I hope I got the drug indications close to right. It is not easy to match the patient with the right drug indication. I usually wind up asking the pharmacist. The one thing I remember is that the “W” in Wegovy is usually a “Winner” for patients with CVD.
One of the problems with the incretins is that the weight loss is accompanied by muscle loss. Amylin is secreted with insulin and activates the activin receptor in muscle and adipose tissue. Activin decreases muscle growth. Myostatin also binds to the activin receptor and also decreases muscle growth. A myostatin genetic mutation is responsible for the super-sized muscles in Blue Belgian cattle. Since activin and myostatin decrease muscle growth, blocking their action on the activin receptor increases muscle mass, improves insulin sensitivity and reduces body fat. Consequently, activin receptor blocking agents are being developed to reduce the loss of skeletal muscle mass produced by incretin mimetics.
I know some clinicians think that patients should lose weight the old-fashioned, exercise-and-diet way. I agree, but many folks just cannot do it, and waiting for it to happen is like the Beckett play, Waiting for Godot. The dude never shows. Medicine is not a morality play. A patient’s arteries do not care how the glucose level got normal… as long as it got normal.
So, here are the Rules:
- Learn about the incretin drugs and how to use them.
- Medicine is not a morality play. It is not as important how someone gets healthy as long as they do.
References
1. Kushner RF, Jastrehoff AM, Ryan DH. Current and Future Medications for Obesity Treatment. JAMA. 2025 Nov 4;334(17):1551-1552. PMID: 40932726
#obesity #diabetes #weightloss #weightlossdrugs
Thank you, Drs Stein and Rubin, for reading the blog and for your kind comments.
Thank you, Dr Thompson. This really resonated with me!
Mechanism of action clarity helps with the bedside conversation. I have always remembered the incretin definition, but your GLP‑1 vs GIP contrast and W=Wegovy=Winner makes it even easier for me to remember.
I appreciate your honesty about needing the pharmacist. I am finding that the “what is approved for whom” changes much faster than my neuron models. Do you have a simple workflow you teach residents and fellows for e.g. diabetes + ASCVD risk reduction vs obesity + established CVD vs obesity + OSA, so we don’t get paralyzed by the brand complexity?