An emerging weight loss medication called semaglutide is catching the headlines. These medicines are originally used for type 2 diabetes treatment but their weight loss effect is stirring up public interest, as well as the interest from pharmaceutical companies which are exploring their use as weight loss medicines. Due to the discovery, demand for the drugs has soared, thus creating global supply woes and shortage of the medication for patients who are in need of treating type 2 diabetes [1]. As a result, Novo Nordisk announced on May 23, 2023 that it would temporarily stop advertising its diabetes medication Wegovy, which was approved for weight loss in 2021, to prevent high demand from leading to a shortage.

You may ask, what are semaglutides? Are they safe? Should you consider it? This post aims to summarize the current findings and status of this drug and inform the readers about their choices.

WHAT’S SEMAGLUTIDE AND GLP-1?

Semaglutide belongs to a class of medications known as GLP-1 analogue (glucagon-like peptide-1 receptor agonists). GLP-1 is a gut hormone produced by the gut and brain in response to food ingestion. It not only stimulates the secretion of insulin to lower blood sugar and inhibits glucagon secretion, but also increases beta-cells in the pancreas by acting as a growth factor [2], making it highly useful in diabetes treatment.

GLP-1 promotes satiety through receptors in the brain stem and hypothalamus, thereby reducing food intake [3, 4]. In the stomach, GLP-1 inhibits gastric emptying, acid secretion and stomach motility, which not only reduces glucose spike with food ingestion, but also decreases appetite [5].

In summary, the semaglutide medication mimics the actions of GLP-1 by targeting the brains, stomach, pancreas, liver, and bone. As a result, there is a decrease of appetite, reduced gastric motility and emptying, increased insulin secretion, reduced hepatic glucose production and lipogenesis, and increased bone formation.

MAJOR MARKET PLAYERS OF SEMAGLUTIDE DRUGS

The major semaglutide medications that have been used to treat type 2 diabetes include (Table 1):

Table 1. Major manufacturers and their semaglutide products for type 2 diabetes.

Two drugs have been approved for chronic weight management. They are both from Novo Nordisk (Table 2):

Table 2. Major manufacturers and their semaglutide products for weight loss.

Meanwhile, Eli Lilly is applying to FDA for its diabetes drug Mounjaro to be approved for use in weight loss.

For a comparison of these drugs with regard to their dosage, form of delivery, approved population, and their effects, please refer to this website. 

BENEFITS ON WEIGHT LOSS

Studies have shown effective weight loss by taking these medications.

In one study, overweight and obese adults with type 2 diabetes who took Mounjaro weekly, and adopted a healthier lifestyle, lost 16% of their body weight on average over 72 weeks (Eli Lilly announcement. Publication source unclear).

In a double-blind trial enrolling 1961 adults with BMI of 30 or greater, body weight reduction of over 17% over a 68-week period was achieved using a semaglutide drug [6].

According to Novo Norkisk’s study, Ozempic showed an average of 12.5-14.1 lb of weight loss by 40 weeks in adult patients with type 2 diabetes [7].

Ozempic® weight loss effect across dosess in adult type 2 diabetes patients. [7]

Primary research findings showed that Wegovy lowered the patients’ 10-year risk of heart attack and stroke from 7.6% to 6.3% after one year on the medication, and the users experienced lower blood pressure, total cholesterol, triglycerides, and blood sugar levels [8]. It should be noted, however, that this was only a primary study done among 93 patients and was not peer-reviewed. Novo Nordisk is expected to release results from its 5-year trial looking into the health impact of its semaglutide drugs later 2023 [9].

SIDE EFFECTS OF SEMAGLUTIDES

Similar to most medications, the semaglutide drugs have their own share of side effects. Here we list some commonly reported side effects, but take note that some of these are from anecdotal sources [10]:

• Feeling repulsed by your favorite foods; nausea
• Diarrhea
• Tasting metals
• Hair loss
• Ozempic face/body: saggy skin
• Rebound
• Enlarged intestine
• Thyroid cancer risk (rodent study)
• Other health conditions

At least two clinical studies have shown that around 40% of the weight loss come from lean tissues [6, 11].

Although any weight reduction will see lean body weight loss, the implication of such high percentage of lean tissue loss calls for further research on its impact to the overall wellbeing of the subjects receiving the treatment.

The financial repercussion is worth considering. When using as a diabetes treatment, the drugs are supposed to be taken for life, creating a massive financial burden (~$1000USD/month).

Stopping the medication caused rebound of 67% of the lost weight in 120 weeks. The cardiometabolic improvements reverted towards baseline [12].

THE BOTTOM LINE

• GLP-1 analogue is a class of promising drugs that can be effective for weight loss for people with Type 2 diabetes, overweight, and obesity.
• Most GLP-1 analogue drugs are long-term medications indicated for Type 2 diabetes, not healthy, non-obese individuals. Currently (up to 2023) only Wegovy and Saxenda are approved by the FDA for chronic weight management.
• Most studies did not last for more than 2 years. The long-term health effects are unknown.
• There are negative effects associated with the drug.
• The weight loss can cost a significant amount of loss in lean body tissues, but the exact implication is unknown.
• The GLP-1 analogue drugs are meant to be taken for long-term. Rebound happens after cessation of the medication.

For further reading, please see:

• Ozempic
• Ozempic Side Effects
• Ozempic Lawsuit

REFERENCES

[1] NBCNews

[2] Buteau, J. (2008). GLP-1 receptor signaling: effects on pancreatic β-cell proliferation and survival. Diabetes & Metabolism 34, S73–S77. 10.1016/S1262-3636(08)73398-6.

[3] Flint, A., Raben, A., Astrup, A., and Holst, J.J. (1998). Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J. Clin. Invest. 101, 515–520. 10.1172/JCI990.

[4] Larsen PJ, Tang-Christensen M, Holst JJ, Orskov C. Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem. Neuroscience. 1997 Mar;77(1):257–270.

[5] Nauck MA, Niedereichholz U, Ettler R, Holst JJ, Orskov C, Ritzel R, Schmiegel WH. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol. 1997 Nov;273(5 Pt 1):E981–E988

[6] Wilding, J.P.H., Batterham, R.L., Calanna, S., Davies, M., Van Gaal, L.F., Lingvay, I., McGowan, B.M., Rosenstock, J., Tran, M.T.D., Wadden, T.A., et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 384, 989–1002. 10.1056/NEJMoa2032183.

[7] Novomedlink

[8] Ghusn, W., Anazco, D., Fansa, S., De La Rossa, A., Nicolalde, B., Cifuentes, L., Hashem, A., Campos, A., Gala, K., Hurtado, M.D., et al. (2023). Cardiovascular Risk Improvement with Semaglutide in Patients with Overweight and Obesity: A Multi-centered Study. In ECO 2023.

[9] Reuters news

[10] Forbes Health

[11] McCrimmon, R.J., Catarig, A.-M., Frias, J.P., Lausvig, N.L., Le Roux, C.W., Thielke, D., and Lingvay, I. (2020). Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised controlled clinical trial. Diabetologia 63, 473–485. 10.1007/s00125-019-05065-8.

[12] Wilding, J.P.H., Batterham, R.L., Davies, M., Van Gaal, L.F., Kandler, K., Konakli, K., Lingvay, I., McGowan, B.M., Oral, T.K., Rosenstock, J., et al. (2022). Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obesity Metabolism 24, 1553–1564. 10.1111/dom.14725.