About 1 in 7 users (14.6%) of injectable GLP-1 receptor agonists (RAs) have taken or are taking them at lower doses than those approved by the FDA, and many decided to do so without clinician input, a new survey found.

The most common reasons for GLP-1 RA microdosing are to manage tolerability, save money, and transition from weight loss to weight maintenance, according to the survey by Evidation, a California-based company that gathers healthcare information directly from members via its app.

The firm is conducting patient-consented research with over 160,000 members actively managing their weight and related health conditions. It sent a survey on experiences with and perceptions of GLP-1 RA microdosing to a subset of those research participants, and its findings are based on responses from 60,157 of them. Of respondents (mean age, 44.5 years, 78.6% women; 77.3% White individuals), 6574 were taking an injectable GLP-1 RA, 667 were taking a pill, 49,070 had never taken a GLP-1 RA, and 3846 had taken one in the past but had stopped.

About half of those who microdose started on a standard GLP-1 RA regimen, according to the survey. About half the people who microdose use compounded versions of the drugs, it found.

“Evidation’s microdosing survey reveals important aspects of real-world usage currently invisible through EHR [electronic health record] or claims data. Microdosing is just one example of how the demand and market for metabolic therapies is larger, more varied, and more dynamic than what prescribing or billing data can show,” said Leslie Wilberforce, CEO of Evidation.

GLP-1 RA microdosing comes in several forms: starting the drug at a dose lower than the recommended therapeutic amount, increasing the dose by smaller amounts than usual, lengthening the time period between doses, reducing the dose for weight maintenance, and slowly stopping its use, said Ghazanfar “Sunny” Khan, MD, MSPH, chief medical officer of Evidation.

Many Patients Act Alone

Almost 38% of 591 respondents who were actively microdosing said they made the decision on their own. That compares with 42.1% who decided in collaboration with their healthcare clinician, 14.7% who said they were exactly following their clinician’s recommendation, and 4.1% following a set plan by a telemedicine service. Among 371 respondents who were on a standard GLP-1 RA regimen but who had previously tried microdosing, 32.6% had made the decision to microdose on their own.

The majority (60.2%) of 5611 respondents who used the standard regimen and never microdosed reported they obtained their GLP-1 RA from their current healthcare clinician.

The situation was far different among respondents who were actively microdosing — only 39.8% of them said they got their medication from their current healthcare clinician. Almost 24% reported getting their GLP-1 RA from a telehealth service. Less common sources included med spas, weight-loss clinics and directly from the manufacturer.

Telemedicine services typically offer lower-cost compounded versions of GLP-1 RAs, making them an attractive option for patients, noted an article in Medscape Medical News.

When asked about their most trusted source of information on microdosing, a larger percentage of GLP-1 RA users answered social media (26.8%) and online research (24.4%) than answered their healthcare clinician (20.3%).

Awareness of microdosing appears to be widespread. Almost 28% of respondents who’d never taken a GLP-1 RA expressed interest in the practice, motivated by cost; concern about possible side effects, such as loss of muscle mass; and desire for dosing flexibility, the survey found.

Variation in Drug Response

Patients respond very differently to GLP-1 RAs, Daniel Drucker, MD, senior investigator at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, told Medscape Medical News. “We see this in clinical trials and in the real world. Some people will lose 25% of their body weight on GLP-1 medications, and their neighbor is very disappointed because she hasn’t lost any weight on the same dose,” he said.

This means that “not everyone will need the same dose or even the highest dose, so there may well be people who would do fine with lower doses,” said Drucker, a professor in the Division of Endocrinology at the University of Toronto, Toronto, Ontario, Canada.

Currently, there is no reliable way to figure out in advance who will respond to which dose, he noted.

Although anecdotal accounts are a “valuable source of information, rigorous scientists need more to support a given hypothesis,” Drucker said.

He suggested that a randomized clinical trial should be conducted to investigate lower vs higher doses. Until such a trial has been conducted, “we have to regard these accounts as hypothesis-generating but not as a way of establishing new dose recommendations,” he said.

Khan reported being an employee of Evidation, which funded the research. Drucker reported serving as a speaker within the past 12 months for Novo Nordisk Inc and Eli Lilly Inc and as a consultant to Alnylam, Amgen, AstraZeneca, Crinetics, Eli Lilly, General Medicines Inc, Kallyope, Pfizer Inc, Protagonist Therapeutics, and Sanofi Inc. He reported holding nonexercised options in Kallyope. GLP-2 is the subject of a patent license agreement between Takeda Inc and the University of Toronto, Toronto General Hospital, and Drucker.

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).