By Dr. Matthew Auman
Throughout the practice of medicine, there are moments when new classes of medications fundamentally transform patient care. This happened with antibiotics from the 1940s to the 1960s, and again with groundbreaking therapies for heart disease from the 1980s through the early 2000s. Today, we’re experiencing another pivotal shift with life-changing treatments for diabetes and weight management. Over the past decade, several injectable medications have emerged that help reduce appetite and support significant weight loss for many patients. These drugs are commonly known as GLP-1 medications—or more precisely, incretins.
Incretins or GLP-1 medicines are modified forms of a very short acting hormone made by the human gut – called endogenous or native GLP-1. Native GLP-1 only lasts a few minutes in the blood, after being released from the intestine during meals. Scientists at two large pharmaceutical companies have found ways to modify native GLP-1 to make it last longer – with about one week of effectiveness. The first of the weekly GLP-1 medications that caused weight loss was semaglutide – sold as Ozempic for diabetes or Wegovy for weight loss. Wegovy has now been approved for forms of non-alcoholic fatty liver disease (now called M.A.S.H.)
Semaglutide was a game-changing medication for many patients. Longer-term studies show that semaglutide lowers both the risk of heart attack and stroke in those patients with diabetes1. Another trial showed that the heart and circulatory system benefit wasn’t limited to those with diabetes. The SELECT trial of semaglutide in non-diabetics with heart disease showed a significant decrease in heart events as well2.
Semaglutide has significant benefits, but also some risk of worsening diabetic eye disease and significant GI side effects. More recently, another medicine – tirzepatide – from a competing company, was approved. Tirzepatide was first approved for diabetes as Mounjaro, and then for weight loss as Zepbound. The trial testing cardiac health with tirzepatide in diabetes has not yet announced results as of this writing.
Tirzepatide has led to significantly more weight loss than semaglutide, as well as being better tolerated by most patients. There is less desire to eat with tirzepatide, but for most patients there is no food aversion or nausea like with semaglutide. This has been somewhat surprising, as tirzepatide activates another incretin receptor in the body called GIP, as well as GLP-1. Tirzepatide has now been approved for moderate to severe sleep apnea. If you snore significantly at night, have extra tissue on the front of your neck, or wake up with a headache consistently, being tested for sleep apnea is wise. The sole treatment for moderate to severe sleep apnea now can sometimes be the weight loss medicine Zepbound. GLP-1 medications, or more accurately incretins – have been life changing medicines for many patients. I love seeing patients who couldn’t exercise before due to asthma or knee pain lose weight and then become more active with incretin medicines.
If a patient doesn’t exercise at all when decreasing food intake, then there can be both fat loss and muscle loss from incretin medicines. It is extremely important, when using GLP-1 medications, to increase physical activity as much as possible. Muscle loss – called sarcopenia – usually happens with age. Sarcopenia happens faster with rapid weight loss unless there is consistent exercise. Strength (resistance) training twice weekly and some form of physical activity like walking, almost daily, is vital if at all possible while on incretin medications.
Many people, when not taking any medication that controls appetite, will have increased appetite due to a higher activity level. GLP-1 medications help blunt this increased appetite from exercise. This ability to exercise without increased appetite is one of the best aspects of incretin medications.
Also, many patients affected by obesity have knee pain that prevents most exercise. The good news is that initial weight loss with GLP-1 medication can lessen this pain
significantly. Exercise can then begin in small amounts. As further weight is lost, longer or more intense exercise can be tried. Exercise doesn’t have to be at a gym. There are many home exercise bikes available for around $200. This is much cheaper than most other home exercise equipment. Using your arms to lift three-to-five-pound weights while using a stationary bike 20 minutes a day is excellent exercise. I encourage patients to watch their favorite shows on their phone while exercising on equipment at home, when safe. The distraction of smart phones can help people ease into regular exercise, and even look forward to it.
The main side effects from incretin or GLP-1 medications that I have seen are gastrointestinal. There is frequently constipation at higher doses of both semaglutide as well as tirzepatide. There are ways to treat this – but I recommend fiber in the form of wheat dextrin (brand name Benefiber – but also generic) daily. Wheat dextrin fiber completely dissolves in warm drinks like coffee – it just needs to become part of a regular routine. Starting fiber, and increasing water intake daily to nearly three liters for women and nearly four liters for men3, before starting GLP-1 medicines, is important.
Rapid weight loss of any form seems to increase the risk of gallstones. Gallstones themselves can be painful but can also cause a severe (and very painful) condition called gallstone pancreatitis. It is important to inform your provider if you are aware you have gallstones before starting an incretin medication. Ideally, it would be best for gallbladder removal before starting any incretin medicine. New onset heartburn can be an indication of gallstones, especially if there are other risk factors like obesity or family history of gallstones.
Incretin medicines have helped many of my patients lose weight and improve overall health dramatically. This class of medicines is one of my favorites in my practice with Wellstone in Temple, Texas.
Sources:
- Marso, S. P., et al. (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine, 375(19), 1834–1844. https://doi.org/10.1056/nejmoa1607141
- A. Michael Lincoff et al. (2023). Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. The New England Journal of Medicine, 389(24). https://doi.org/10.1056/nejmoa2307563
- Heymsfield, S. B., & Shapses, S. A. (2024). Guidance on Energy and Macronutrients across the Life Span. New England Journal of Medicine/the New England Journal of Medicine, 390(14), 1299–1310. https://doi.org/10.1056/nejmra2214275