The New Age of New Year’s Resolution!

January of 2023 may be remembered  as the month that  an overwhelming number of people requested weight-control pills from their doctors.  The leading impetus for this phenomenon appears to have been fueled by several Hollywood celebrities who have acknowledged the use of Ozempic as their trendy weight loss remedy. In this article we have selected three popular prescribed weight loss medications in the US. These include but are not limited to  Ozempic, Contrave and Metformin. For each drug we have cited the mechanism of its  action, preferred indications, common side effects, and the most dreaded side effects.

CONTRAVE

Contrave is an FDA-approved medication designed for weight loss in adults who have a BMI greater than thirty or a BMI greater than twenty-seven with at least one weight-related comorbidity, such as hypertension, type 2 diabetes mellitus, coronary heart disease, and dyslipidemia (i.e., high cholesterol or high triglycerides). Before taking Contrave you must be qualified to receive it? Please use the enclosed Body Mass Index  conversion chart  to calculate your BMI. I trust that you can figure out the rest on your own! If your BMI is less than 27 you would be able to manage your weight  by lifestyle modifications and regular workouts! I believe that you can do it without the meds if you give it your best!

A Combination Drug…

Contrave is a combination medication composed of naltrexone and bupropion that targets both the appetite-regulating center of the hypothalamus and the mesolimbic dopamine reward system of the midbrain. This system responds to  rewarding and pleasant stimuli by releasing dopamine, that in turn mediates a feeling of pleasure. The weight loss effects of Contrave must be due to reduction in craving and enhancement of satiety. However, the exact neurochemical weight loss mechanism of action of Contrave is not fully understood. 

Isolated Functions of Naltrexone and Bupropion

Naltrexone has been on the market since the 1970s. It has been used  for management of opiate and alcohol use disorders, by reducing cravings associated with their use. It performs this function by blocking  the opioid receptors that modulate release of dopamine in the mesolimbic system. 

Bupropion  has been approved by the FDA since 1985, and it is commonly used in the treatment of depression. It acts via dual inhibition of norepinephrine and dopamine reuptake in the midbrain. This leads to increased levels of dopamine and norepinephrine. 

Contraindications of Contrave

Contrave is contraindicated in patients with uncontrolled hypertension, bulimia/anorexia nervosa, and seizure disorders. It should not be used in patients taking other bupropion-containing medications, opioids, or monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive emergencies.

Common Side Effects of Contrave

Common side effects of Contrave include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. It should not be used with drugs that are metabolized by CYP2D6 (a cytochrome P-450 family member) or with medications that lower seizure thresholds (e.g., bupropion, tricyclic antidepressants, and antipsychotics) or neurotoxic medications (e.g., cisplatin, paclitaxel, and vincristine).

A last resort medication…

Contrave is indicated after lifestyle modifications have been failed, and after unsuccessful attempts in treating the underlying causes of obesity.

Semaglutide (Ozempic)

Semaglutide, also called Ozempic, is a medication for treating type 2 diabetes mellitus. It is a glucagon-like peptide-1 (GLP-1) receptor agonist that helps increase insulin secretion in response to glucose, reduces glucagon secretion, slows gastric emptying, and impacts the brain’s appetite and calorie regulation areas.

Ozempic is used as an add-on therapy or alternative monotherapy in patients who cannot tolerate metformin or when lifestyle modifications and metformin treatment have failed. It is preferred for patients with a high risk of atherosclerotic cardiovascular disease, for weight loss, or in patients with very high hemoglobin A1C (HbA1C) levels (e.g., 9 to 10%). It can also be used in chronic weight management, especially in patients with a BMI of more than 30, or BMI of more than 27 with weight-related comorbidities such as hypertension, diabetes, or lipid disorders. 

To manage weight loss, Ozempic is employed in one weekly  dose that  is increased gradually over a 16-week period from 0.25 mg to 2.4 mg. Discontinuation of Ozempic is mandated if patients do not lose a minimum of 5% of their baseline weight within the first three months of therapy. For instance, a 250 Ibs  male patient who has been on Ozempic for 90 days, must have minimally lost 12.5 Ibs, otherwise, he should no longer continue with the medication.   

Side Effects of Ozempic

The common side effects of Ozempic  include gastrointestinal disturbances such as abdominal pain, constipation, diarrhea, nausea, vomiting, decreased appetite, dyspepsia, fatigue, headache, pancreatitis, and nasopharyngitis.

Potential dreaded Side Effect: Due to the risk of developing medullary thyroid cancer (MTC) in rodents, Ozempic is contraindicated in patients with a personal or family history of MTC or Multiple Endocrine Neoplasia syndrome 2 (MEN 2). Regular monitoring of serum calcitonin or thyroid ultrasound is recommended for early detection of MTC in patients taking Ozempic.

Metformin

Metformin is the oldest anti type 2 diabetic medication in the market. Metformin is commonly used when dieting and exercise alone are not sufficient to manage hyperglycemia. By decreasing hepatic glucose production, intestinal absorption of glucose, and improving insulin sensitivity, metformin helps increase peripheral glucose uptake and utilization. Additionally, it can be used off-label for antipsychotic-induced weight gain, gestational diabetes, prevention of type 2 diabetes, and ovarian hyperstimulation syndrome prevention in patients with polycystic ovary syndrome, or those  undergoing in vitro fertilization.

Metformin has common adverse reactions such as gastrointestinal effects (nausea, diarrhea, dyspepsia, flatulence, vomiting, and abdominal pain), lactic acidosis, and vitamin B12 absorption interference/deficiency. The latter can lead to anemia and neuropathy. Metformin-associated lactic acidosis is characterized by elevated blood lactate levels, anion gap acidosis, and an increased lactate to pyruvate ratio. The  high lactate to pyruvate ratio indicates low mitochondrial energy production, and as a result hypothermia, and hypotension. High levels of serum lactic acid may potentially cause severe  electrolyte imbalance, and heart rhythm abnormalities. 

Up until introduction of the glucagon-like peptide-1 (GLP-1) receptor agonists such as Ozempic, metformin was the only anti-diabetic medication that had the ability of keeping weights under control. It is noteworthy that within the past several years there has also been a surge of interest in metformin as an anti-aging agent. Given its long history of performance, metformin is by far the best of all time weight reduction medications, in particular, for type 2 diabetics.

Furthermore, given our sedentary lifestyles and our easy accessibility to food supplies, overweightness, and obesity, and as a result glucose intolerance, happens to be a curse for so many of us. For the latter reason metformin happens to be one of the commonly used medications in the world. 

Suggested References

Metformin: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520185/

Contrave: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771085/

Semaglutide: https://pubmed.ncbi.nlm.nih.gov/33567185/

Glucagon-like peptide 1 (GLP-1): https://www.ncbi.nlm.nih.gov/books/NBK551568/

Acknowledgement: I would like to extend special thanks to my personal research assistant, Mrs. Felicia Raju (Dr. Raju, effective May of 2023) for her contributions to this article and in particular for researching and writing about the side effects and mechanism of action of each cited drug.