By Mofolorunso Adekunle Enigbokan
Certain hormones help to regulate our blood glucose ( sugar ) levels. Prominent among them are Insulin (from the Pancreas ), Glucagon ( from the Pancreas ), Substance P ( from neurons ), Glucagon-like peptide ( GLP-1 ) and Glucose insulinotropic polypeptide ( GIP ). GLP-1 and GIP are called Incretins and they are produced in the gut and in the brain. Incretin receptors are found in many parts of the body, including the gut, the brain and the bones.
When we eat, GIP and GLP-1 are released in the gut. They bind to, and activate, their receptors, thus generating impulses (chemical/electrical instructions ) that are sent to the pancreas, the stomach, the intestines, the brain and the bones. Based on those impulses, the pancreas will release Insulin which will then cause a reduction in blood sugar levels. Those Incretin-generated impulses will also induce the secretion of a hormone called Substance P from some neurons (nerves) in the gut. The Substance P will, in turn, stimulate Insulin secretion from the pancreas and that will result in a further decrease in blood sugar levels. Of course, that will be beneficial to a patient who has diabetes.
When GLP-1 and GIP activate their receptors in the brain, the impulses that are generated will signal a reduction in appetite for food. Those impulses ( instructions ) will also be relayed back to the stomach, telling the stomach to reduce the rate at which it moves food out of the stomach into the small intestine. The retention of food in the stomach for a longer period of time will make an individual feel full ( satiety ) and they will consume less food. A decrease in appetite, coupled with a quicker and longer feeling of fullness, will yield a reduction in the quantity and frequency of food consumption and that will invariably result in weight loss.
An individual who is “addicted” to drugs, smoking, alcohol, sex, shopping, food or hoarding maintains that behavior because it is pleasurable; it makes them feel good or satisfied. It is a reward system. That reward system is controlled by two chemicals in the brain. One is called Dopamine and the other is called Gamma-Aminobutyric acid ( GABA ). Dopamine stimulates the reward center while GABA inhibits the reward center. When GLP-1 and GIP activate their receptors in the brain, the generated impulses ( instructions ) will decrease the release of Dopamine ( stimulator ) in the reward center while increasing the release of GABA ( inhibitor ) in the reward center. If the addictive behaviour is no longer being rewarded with pleasure or satisfaction, the individual will have the tendency to cease indulging in that behaviour.
GLP-1 and GIP are naturally occurring hormones. Unfortunately, their beneficial effects do not last long because the body also produces an enzyme that breaks down GLP-1 and GIP. That enzyme is called Dipeptidylpeptidase-IV ( DPP-IV ). So, in order to get and prolong all of the above-described beneficial effects of the Incretins, medications that can activate GLP-1 and GIP receptors, while being resistant to the destructive actions of DPP-IV, were made. As a class, those medications are referred to as Incretin mimetics. That is, they mimic the actions of Incretins ( GLP-1 and GIP ) at their receptors. Examples of Incretin mimetics are Exenatide ( Byetta; Bydureon ), Lixisenatide ( Lyxumia ), Liraglutide ( Victoza ), Albiglutide ( Tanzeum; Eperzan ), Dulaglutide ( Trulicity ), Semaglutide ( Ozempic; Wegovy; Rybelsus ), Tirzepatide ( Mounjaro ), Retatrutide ( 3G ) and Danuglipron.
All of these drugs are effective in managing Type 2 diabetes and they all produce weight loss by activating GLP-1 receptors as mentioned above. Tirzepatide ( Mounjaro ) activates both GLP-1 and GIP receptors while Retatrutide interacts with GLP-1, GIP and Glucagon receptors. Hence, Tirzepatide and Retatrutide produce more weight loss than all of the other Incretin mimetics.
The Incretin mimetic that has been studied the most is Semaglutide. Preliminary studies in animals and anecdotal reports from human beings strongly suggest that Semaglutide reduces alcohol drinking, alcohol dependence and nicotine use. Preclinical research has shown that individuals on Semaglutide demonstrated a reduced craving for smoking, gambling, shopping, coffee, opiates ( narcotics ) and previously uncontrolled eating.
Now, there is a condition called PCOS ( Polycystic ovary syndrome ). It afflicts women. It is characterized by an increased level of the male hormone ( testosterone ), acne, obesity ( excess body weight ), fatigue, facial hair growth, infertility, Insulin resistance and irregular menstruation. Metformin, a drug that is used to control diabetes, helps in managing PCOS a little bit because it helps to curb the Insulin resistance. However, dramatic improvements are observed when PCOS patients are placed on either Semaglutide or Tirzepatide. Menstrual cycle becomes regular, weight is lost ( 45 lb in 7 months ), fertility is regained, facial hair growth is attenuated and cravings for carbohydrates, sugar and high-fat foods are all but eliminated.
In conclusion, for individuals who have diabetes mellitus Type 2, obesity, addictive behaviours and/or PCOS, help is on the horizon in the form of Semaglutide and Tirzepatide.
- Dr. Enigbokan is a Professor of Pharmacology and Toxicology at the College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas.
