Diet gun

Slowing down metabolism, weight gain and body fat redistribution are side effects of many drugs on the market.

These side effects increase the risk of developing additional diseases such as type 2 diabetes, metabolic syndrome, cardiovascular disease, dyslipidemia, non-alcoholic steatohepatitis (NASH), cancer.

The following is a brief overview of the drug categories, their effect on weight gain and, where possible, the mechanism that causes it (in simple terms).

DRUGS RELATED TO WEIGHT GAIN

Antihypertensive drugs

Antihypertensive drugs include beta-blockers and calcium channel blockers.

The use of beta-blockers is associated with a weight gain of 1.2 kg and up to 4 kg or more after one year of treatment. The greatest weight gain occurs in the first months of treatment.

Their mechanisms of influence on weight are a decrease in metabolism and inhibition of lipolysis.

Beta-blockers cause abdominal fat accumulation that is associated with abnormalities in carbohydrate metabolism.

Of the beta-blockers, only nebivolol causes lipolysis, reducing the size of lipids and adipocytes.

Calcium channel blockers are weight neutral and do not show adverse effects on glucose and lipid metabolism.

Only flunarizine (used for migraines) is associated with increased appetite and weight gain of up to 4 kg.

Diabetes Medications

Insulin, sulfonylureas (SUs), and thiazolidinediones (TZDs) used in the management of diabetes can cause significant weight gain.

Metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors are considered weight neutral.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor analogs (GLP1RAs) are associated with moderate weight loss.

The potent anabolic effect of insulin can increase protein synthesis and inhibit lipolysis and proteolysis, resulting in a small increase in lean body mass.

Adding metformin to insulin therapy reduces the effects of insulin on body weight by reducing energy intake.

Weight gain from sulfonylureas is approximately 4 kg during the first year of treatment.

Thiazolidinediones cause weight gain ranging from 1.5 to 4 kg during the first year of treatment. Typically, weight gain is due to fluid retention, promotion of lipid storage, and lipogenesis.

Psychotropic Drugs

Obesity is up to three times more common in patients with psychiatric disorders, and obese individuals also suffer from psychiatric illnesses more frequently than those of normal weight.

The interaction between obesity and psychiatric illness involves an accumulation of adverse metabolic behaviors such as unhealthy diet and insufficient physical activity.

The pathophysiological processes that lead to psychiatric illnesses share common brain pathways with those that lead to unwanted weight gain, such as obesity, metabolic syndrome, and cardiovascular disease risk factors.

Weight gain, usually in the first month after starting treatment, is a strong predictor of long-term weight gain.

Antiepileptic drugs

Many treatments for epilepsy are associated with weight gain.

Valproate and carbamazepine, pregabalin, and gabapentin cause weight gain.

Antiepileptic drugs that do not affect weight include lamotrigine, levetiracetam, and phenytoin.

Antiepileptic drugs that are associated with weight loss include felbamate, topiramate, and zonisamide.

The mechanism of valproate in causing weight gain is primarily related to neuropeptides that regulate appetite within the hypothalamus. Valproate also increases leptin resistance, and free fatty acids increase, resulting in insulin resistance, hyperglycemia, and type 2 diabetes.

Antidepressants

The magnitude of weight gain during antidepressant treatment varies significantly by class.

Tricyclics

The greatest potential for weight gain has been demonstrated with the tricyclics amitriptyline and nortriptyline, both in the acute and maintenance periods of depression treatment.

Serotonin

During initial serotonin treatment, there is a small weight loss, but as treatment continues into chronic treatment, weight gain is observed.

Paroxetine is considered to cause the greatest long-term weight gain.

Bupropion

Bupropion reduces appetite and food cravings and helps with weight loss. Buprione in combination with naltrexone is used as an anti-obesity drug.

Lithium

Lithium increases weight by more than 5% of the initial body weight without the exact mechanism that causes it being known. It is likely related to the center of the hypothalamus that controls appetite, increased thirst and increased intake of high-calorie drinks, changes in food preferences and its effect on thyroid function.

Antipsychotic drugs

Antipsychotic drugs are taken for psychosis but also for bipolar disorders, for attention deficit disorder and for the treatment of dementia in the elderly.

They are divided into Typical (conventional) and Atypical (2nd generation – SGAP) Antipsychotics

Up to 80% of patients taking antipsychotic drugs experience weight gain that exceeds their ideal body weight by 20% or more.

The greatest weight gain is mainly associated with olanzapine and clozapine.

The effects of antipsychotics on weight gain appear to be more pronounced in individuals with normal body weight at the start of treatment and more so in women.

Patients who have never taken medication gain significantly more weight than those who have taken antipsychotics in the past.

SGAPs promote lipogenesis and enhance the antilipolytic effects of insulin, favoring lipid accumulation and causing insulin resistance. This results in glucose dysfunction and an increased risk of metabolic syndrome and type 2 diabetes.

DRUGS ASSOCIATED WITH WEIGHT GAIN AND BODY FAT DISTRIBUTION

Lipid-Lowering Drugs

Human monoclonal PCSK-9 inhibitors (alirocumab and evolocumab) have demonstrated significant and sustained reductions in LDL-cholesterol levels, as well as significant reductions in major cardiovascular events.

PCSK9 variants associated with lower LDL cholesterol have been associated with increased fasting glucose levels, increased body weight and increased waist-to-hip ratio, as well as an increased risk of type 2 diabetes.

Therapies that reduce the rate of VLDL secretion such as mipomersen are associated with an approximately fourfold higher risk of hepatic steatosis.

Treatment with inhibitors (lomitapide) of the microsomal triglyceride transfer protein (MTP) that transports the lipid droplet to newly formed VLDL and chylomicron particles is associated with intrahepatic fat accumulation up to six times greater than mipomersen and more severe elevations in transaminase levels.

Corticosteroids

Chronic corticosteroid therapy shows weight gain in up to 70% of all patients.

Weight gain associated with glucocorticoid therapy is greater than 10 kg in approximately 20% of patients during the first year of treatment.

Inhaled corticosteroids and single injections have no effect on body weight.

Glucocorticoids may cause an increase in food intake and a preference for low-nutrient, high-calorie foods.

Glucocorticoids reduce thermogenesis, thereby affecting metabolic rate.

Chronic glucocorticoid therapy activates the eCB system, which, among other things, is a regulator of food intake and reduces energy expenditure.

Glucocorticoids also affect body fat distribution by increasing visceral fat mass, thereby increasing insulin resistance and the risk of impaired glucose tolerance, diabetes, and cardiovascular disease.

Antiretroviral Therapy

Antiretroviral therapy (HAART) for the treatment of HIV disease causes disorders of fat storage, loss, and distribution (lipodystrophy).

Lipodystrophy is characterized by loss of subcutaneous fat in the extremities and face (lipoatrophy) and central or truncal fat accumulation (lipohypertrophy), mainly visceral fat, in the chest and dorso-cervical region, and under the skin as lipomas.

Lipoatrophy occurs in men and women, mainly older people, and is related to the weight they had before treatment.

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