Injectable Weight Loss Drugs: Promises and Pitfalls
Injectable weight loss drugs are the hottest topic on social media and the board rooms of pharmaceutical companies looking to make billions of dollars in future sales. But beneath this glamour is some significant caution.
GLP-1 Receptor Agonists: Semaglutide and Its Weight Loss Potential
Injectable weight loss drugs are known as GLP-1 receptor agonists. The scientific name for the most well-known one is semaglutide, which is marketed under the tradenames Ozempic and Wegovy. In simple terms, these injectable drugs activate the release of the hormone GLP-1 from the gut that goes directly to the brain to tell you to stop eating. These drugs were initially developed to treat type 2 diabetes, but the clinical studies in overweight and obese individuals demonstrated significant weight loss at higher levels (1).
The Difference Between Weight Loss and Fat Loss
Unfortunately, there is a big difference between weight loss and fat loss. Weight loss is the combined loss of stored body fat and lean body mass (i.e., muscle). You want to lose fat but not muscle. Although the weight loss using weekly semaglutide injections was impressive (about 34 pounds) after 68 weeks, you had to go deep into the bowels of the supplementary feature section (Supplementary Index Section 5b) of the article to find that about 40 percent of that weight loss was due to loss of lean body mass. That is not a good sign. It suggests that the injections reduce hunger to the extent that the person has little desire to eat enough protein to maintain muscle mass. In essence, the drug increases the patients' sarcopenia (muscle loss). One of the consequences of sarcopenia is increased frailty.
The Downsides of Stopping Injectable Drugs
Once you stop injecting weight loss drugs, the weight immediately begins to return (2). Not surprisingly, any metabolic benefits initially seen while taking the drug were lost with the weight regain. I suspect that much of the returning weight is primarily as fat since it takes minimal effort to regain lost body fat compared to far greater effort to rebuild lost muscle mass. That data was not studied in the second study and unsurprisingly, both studies were sponsored by the drug company that makes semaglutide. I can understand why they didn’t include the body composition data as it would be bad for marketing.
Zone Diet: The Key to Achieving Lasting Results
Injectable weight loss drugs don't sound too promising if it means you must inject this “wonder” drug for the rest of your life. But is there another way to achieve the same results? I believe the answer is yes if you are following the Zone Diet. Drugs like semaglutide cause the release of GLP-1 and so does intake of dietary protein. So how much protein do you need? The answer is about 30 grams of protein at every meal. Not less, but not more, as excess protein can cause transient insulin resistance. Next, you must balance that protein with the correct amount of low-glycemic carbohydrates to prevent excess insulin secretion, which causes low blood sugar and increases hunger. This concept is the foundation of the Zone diet. That is also why the Zone diet was granted a patent to reduce insulin resistance (3).
Zone Diet: Scientifically Proven Results
The Zone diet has been shown to reduce insulin resistance within days (4). It is insulin resistance that causes you to gain weight. The Zone diet has been shown to help with remission of pre-diabetes (i.e., metabolic syndrome) caused by higher levels of insulin resistance (5). This same eating plan is used by the Joslin Diabetes Center at Harvard Medical School to treat type 2 diabetes caused by severe insulin resistance (6-9). So, what’s the problem with following the Zone diet for life? People seem to believe it is too much effort to balance protein and carbohydrates at each meal.
Zone Foods: A Breakthrough Solution
To address compliance, I applied for another patented technology. This technology enhances the activation of GLP-1 release in the gut to increase satiety dramatically. It does so by slowing the protein absorption rate in the upper region of the small intestine so that more protein reaches the lower part of the small intestine, where specific cells (L-cells) that sense protein and release GLP-1 are concentrated. The result is greater appetite suppression. Furthermore, if you could combine the right balance of protein and carbohydrates into a single food product, no thinking is involved. This breakthrough was the foundation for producing Zone Foods.
Clinical Trials: Zone Foods vs. Injectable Weight Loss Drugs
So, does it work? To answer that question, you must do clinical trials. We published the results in 2017 (10). In subjects consuming Zone Foods for six weeks the total weight loss was virtually the same as the study referenced above using weekly injections of semaglutide. However, the body composition was dramatically different between the two approaches. Those consuming Zone Foods were gaining muscle mass and losing more fat. Although weight change in the control group was about the same as those in the Zone Foods group, it consisted primarily of near equal portions of fat loss and muscle loss, just like the subjects getting their weekly injections of semaglutide. Bottom line, using Zone Foods not only induced greater loss of fat than taking semaglutide injections but also increased muscle mass. Not surprisingly, the use of Zone Foods reduced insulin resistance by 140 percent compared to the control group (10). Now that’s what I call a “wonder drug.”
References
1. Wilding JPH et al. Once weekly semaglutide in adults with overweight or obesity. N Engl J Med 384:989-1002 (2021) doi: 10.1056/NEJMoa2032183
2. Wilding JPH et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obesity and Metabolism 24: 1553-1564 (2022) doi: 10.1111/dom.14725.
3. Sears, B. “Method of and nutritional and pharmaceutical compositions for reduction of hyperinsulinemia.” U.S. Patent No. 6,140,304 (2000)
4. Markovic TP et al. “The determinants of glycemic responses to diet restriction and weight loss in obesity and NIDDM.” Diabetes Care 21:687-694 (1998) doi: 10.2337/diacare.21.5.687.
5. Stentz FB et al. “High protein diet leads to pre-diabetes remission and positive changes in incretins and cardiovascular risk factors.” Nutr Metab Cardiovasc Dis 31:1227-1237 (2021) doi: 10.1016/j.numecd.2020.11.027.
6 Giusti J and Rizzott J. “Interpreting the Joslin Diabetes Center and Joslin Clinic clinical guideline for overweight and obese adults with type 2 diabetes.” Curr Diab Report 6:405-408 (2006) doi: 10.1007/s11892-006-0014-y.
7. Hamdy O. “Diabetes weight management in clinical practice—the Why Wait model,” U.S. Endocrinology 4:49–54 (2008) doi: http://doi.org/10.17925/USE.2008.04.2.49
8. Hamdy O and Carver C. “The Why WAIT program: improving clinical outcomes through weight management in type 2 diabetes.” Curr Diab Rep 8:413-420 (2008) doi: 10.1007/s11892-008-0071-5.
9. Hamdy O et al. “Long-term effect of intensive lifestyle intervention on cardiovascular risk factors in patients with diabetes in real-world clinical practice: a 5-year longitudinal study.” BMJ Open Diabetes Res Care 5:e000259 (2017) doi: 10.1136/bmjdrc-2016-000259.
10. Johnson CS et al. Use of novel high-protein functional food products as part of a calorie-restricted diet to reduce insulin resistance and increase lean body mass in adults: A randomized controlled trial. Nutrients 9:1182 (2017) doi: 10.3390/nu9111182.
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