Strategies for transitioning patients from common weight-promoting medications

A number of commonly used medications can promote weight gain in patients, but there are more weight-favorable alternatives that physicians can help patients transition to.

Beth Mills, PharmD, BCACP, CDCES, CPP, an associate professor of pharmacy practice at Campbell University in North Carolina, and Katie Trotta, PharmD, BCACP, a clinical associate professor of pharmacy practice at Campbell University, presented an overview of medications that possess properties unfavorable to weight — as well as safe and productive medication switching strategies — at the Obesity Medicine Association’s Overcoming Obesity conference.

Mills listed multiple driving factors for medication switches, which can include tolerability, affordability, efficacy, accessibility and a patient’s preference or perception of the medication and dosage.

Frequently used medication classes that often induce weight gain include:

• antidiabetes medications;
• hormonal contraceptives;
• antipsychotics;
• antidepressants;
• anticonvulsants; and
• antihistamines.

Antidiabetes medications

Insulin, thiazolidinediones (TZDs) and sulfonylureas are among several antidiabetes medications that Mills said have negative weight effects.

“We know that insulin can promote weight gain. There is a reversal of the negative energy balance once the insulin is initiated that decreases the amount of glucose that is spilled in the urine. When you’re spilling glucose in your urine, you’re losing calories,” she said.

Fat mass and total body water are further effects of insulin.

Both insulin and sulfonylureas reduce glycosuria and are associated with hypoglycemia or fear of hypoglycemia, which can cause patients to increase food intake, Mills said. Meanwhile, TZDs can decrease leptin levels and increase fat mass and fluid retention.

Mills recommended initiating or switching to weight-neutral or weight-losing medications. She also suggested using a GLP-1 receptor agonist (GLP-1RA) with basal insulin vs. a basal-bolus regimen in patients with type 2 diabetes, and adding a GLP-1RA or metformin to a basal-bolus regimen in patients with type 1 diabetes. However, Mills said the decision to modify therapy should be individualized, with physicians considering factors such as the patient’s current HbA1c level.

Hormonal contraceptives

Mills noted that hormonal contraceptives can promote weight gain. Specifically, progesterone can cause fluid retention, increased appetite, promote deposition of body fat “and has been shown to increase insulin resistance,” she said.

“Progestin-only contraceptives can be weight neutral or cause a modest amount of weight gain, about 2 kilograms over 6 to 12 months,” she said.

Injectable progestin-only contraceptives (medroxyprogesterone) have been shown to increase weight by about 13.7 lbs over 5 years, while “some women will have some androgenic effects from some of the progesterones,” Mills said.

When switching hormonal contraceptives, Mills recommended:

• no gaps between switches, with new medication beginning immediately after the last pill pack is finished;
• informing the patient of possible changes in their menstrual cycles;
• knowing which contraceptives require overlap; and
• to have a backup if the patient chooses not to do an overlap.

Antidepressants

Trotta discussed a number of theories on why antidepressants cause weight gain, one of which being that when people are depressed, they are less likely to eat. That weight loss is then reversed by a properly functioning antidepressant.

“When we look at the medications, the mechanism of the medication can incite some weight gain as well. The more anticholinergic effects that the medication has, generally the more weight gain that we see,” she said, pointing to tricycles, paroxetine and mirtazapine as medications with some of the worst obesity-causing properties or effects.

When switching antidepressants, Trotta noted that selective serotonin reuptake inhibitors (SSRIs) are “probably one of the most common medication classes that you’re going to have to switch between.”

“We know that only one-third of patients have effect with the first SSRI that they try,” she said.

Recommended management strategies when switching between antidepressant classes include tapering the dose of current medication before starting a patient on a new medication. Additionally, SSRIs — with the exception of fluoxetine — can be switched with no overlap, while bupropion and tricycles should be cross tapered over 1 to 3 weeks and 1 to 2 weeks, respectively.

Antipsychotics

“There’s multiple mechanisms associated with weight gain with second-generation antipsychotics,” Trotta said.

Because second-generation antipsychotics work to reduce dopamine, which is associated with appetite control, patients can experience increased appetite.

“They also elicit orexigenic effect due to increases in serum ghrelin and increases in ghrelin signaling,” Trotta noted.

Hyperglycemia and hyperlipidemia are also associated with antipsychotics due to insulin signaling and glucose release.

Antipsychotics that can cause unfavorable weight gain are:

• aripiprazole and lurasidone, which can cause 10% or fewer patients to gain more than 7% weight from baseline;
• amisulpride, asenapine, iloperidone, paliperidone, quetiapine and risperidone, which can cause between 10% to 30% of patients to gain more than 7% from baseline; and
• clozapine, iloperidone and olanzapine, which can cause 30% or more patients to gain more than 7% weight from baseline.

Trotta recommended both the antipsychotic switching tool and antipsychotic dose conversion calculator when switching medications, while promoting switching in patients who are having a “lack of control of their mental illness, and we would do this interprofessionally, utilizing their primary care provider and their psych team.”

Anticonvulsants

Mechanisms for weight gain in anticonvulsants are “not fully elucidated and vary by drug,” Trotta said. “It could be due to impacts on blood glucose. We can have some blood glucose-lowering through insulin stimulation from the antiepileptics, so when we have that increase in insulin and decrease in glucose, it can cause patients to have an increase in appetite.”

According to Trotta, valproic acid, carbamazepine and gabapentin are among anticonvulsants that have significant weight gain, with valproic acid impacting both adults and children, along with those at an elevated body mass index at baseline.

“We do need to be careful when we’re switching our anticonvulsants, especially if we’re using them for epilepsy. That’s when the most caution is going to be needed,” Trotta said, “because we don’t the patients to have unnecessary breakthrough seizures.”

When switching, medication should be tapered over a 4-week period, conducted by decreasing by 25% every week. For patients with epilepsy, Trotta recommended starting new medicine and getting them to their target dose before tapering current medication.

Antihistamines

First- and second-generation antihistamines are both associated with weight gain, though first generations carry a higher risk due to strong anticholinergic properties, Trotta said.

“They are going to block histamine, and then histamine helps to control our hunger hormone. By blocking histamine, we’re having irregularities in our leptin release,” she said.

Trotta recommended second-generation antihistamines due to less risks for weight gain — with loratadine having the least — and to consider both intranasal corticosteroid and allergen avoidance.