Family medicine is a growing field and new developments continue to emerge, making it challenging for the interprofessional team to stay abreast of the latest clinical updates. This article highlights recent advances in family medicine and potential implications for patient care.

WHAT HAPPENS WHEN NEWER WEIGHT LOSS MEDS ARE STOPPED?

The prevalence of obesity is rapidly rising across the globe; within the United States alone, more than one third of adults are living with this chronic disease.^[1] Several anti-obesity medications are approved for the treatment of obesity and should be used in conjunction with lifestyle modification.^[2] Depending on the proportion of weight loss achieved, improvements can be seen in obesity-related comorbidities including reduction in type 2 diabetes and cardiovascular risk.^[3] However, weight regain is a challenge and may be brought about by withdrawal of anti-obesity medication.^[4] In this article, Jaime P. Almandoz, MD, MBA, shares his perspectives on the use and withdrawal of weight loss pharmacotherapy.

Social media outlets are full of stories about celebrities who have lost weight with the new generation of incretin medications. Some of these medicines are approved for treating obesity, whereas others are approved for type 2 diabetes.^[5]

Clinics are full of patients who have taken these medications, with unprecedented improvements in their weight, cardiometabolic health, and quality of life. What happens when patients stop taking these medications? Or more importantly, why stop them? Although these drugs are very effective for weight loss and treating diabetes, there can be adverse effects, primarily gastrointestinal, that limit treatment continuation. Nausea is the most common side effect and usually diminishes over time. Slow dose titration and dietary modification can minimize unwanted gastrointestinal side effects. Drug-induced acute pancreatitis, a rare adverse event requiring patients to stop therapy, was seen in approximately 0.2% of people in clinical trials.

Medications Effective But Cost Prohibitive?

Beyond adverse effects, patients may be forced to stop treatment because of medication cost, changes in insurance coverage, or issues with drug availability. Insurance coverage and manufacturer discounts can make treatment affordable,^[6] but anti-obesity medicines are not covered by Medicare nor by many employer-sponsored commercial plans.

Changes in employment or insurance coverage, or expiration of manufacturer copay cards, may require patients to stop or change therapies. The increased prescribing and overall expense of these drugs have prompted insurance plans and self-insured groups to consider whether providing coverage for these medications is sustainable.

Limited coverage has led to significant off-label prescribing of incretin therapies that are not approved for treating obesity,^[7] and compounding pharmacies selling peptides that allegedly contain the active pharmaceutical ingredients.

Stopping Equals Weight Regain

Obesity is a chronic disease like hypertension. It responds to treatment and when people stop taking these anti-obesity medications, this is generally associated with increased appetite and less satiety, and there is subsequent weight regain and a recurrence in excess weight-related complications.

The STEP-1 trial extension showed an initial mean body weight reduction of 17.3% with weekly semaglutide 2.4 mg over 1 year.^[4] On average, two thirds of the weight lost was regained by participants within 1 year of stopping semaglutide and the study's lifestyle intervention. Many of the improvements seen in cardiometabolic variables, like blood glucose and blood pressure, similarly reverted to baseline.

There are also 2-year data from the STEP-5 trial with semaglutide^[8]; 3-year data from the SCALE trial with liraglutide^[9]; and 5-year nonrandomized data for agents such as metformin, topiramate, and bupropion, that showed durable, clinically significant weight loss for obesity, including an average weight loss of 10.4% after a median follow-up of 4.4 years.^[10] In this 5-year analysis, 428 patients who were treated at an academic weight management clinic, who were classified as obese or overweight, were treated with anti-obesity medication and tracked for an average of 2 years. The main outcome measures were percentage weight loss, weight reduction targets, and other predictors of long-term weight loss. Over the mean duration of 4.4 years, the researchers documented an average weight loss of 10.4%. While 40.2% of patients maintained their weight loss with those medications, about 51% of maximum weight loss was regained.

These data together demonstrate that medications are effective for durable weight loss if they are continued. However, this is not how obesity is currently treated. Anti-obesity medications are prescribed to less than 3% of eligible people in the United States, and the average duration of therapy is less than 90 days.^[11] This treatment length is not sufficient to see the full benefits most medications offer and certainly does not support long-term weight maintenance.

In addition to maintaining weight loss from medical therapies, a recent study showed that incretin-containing anti-obesity medication regimens were effective for treating weight regain and facilitating healthier weight after bariatric surgery.^[12]

Chronic therapy is needed for weight maintenance because several neurohormonal changes occur owing to weight loss. Metabolic adaptation is the relative reduction in energy expenditure, below what would be expected, in people after weight loss. When this is combined with physiologic changes that increase appetite and decrease satiety, many people create a positive energy balance that results in weight regain.^[13] This has been observed in reality TV shows such as The Biggest Loser: It's biology, not willpower.

Unfortunately, many people -- including healthcare professionals -- don't understand how these changes promote weight regain and patients are too often blamed when their weight goes back up after medications are stopped. This blame is greatly misinformed by weight-biased beliefs that people with obesity are lazy and lack self-control for weight loss or maintenance. Nobody would be surprised if someone's blood pressure went up if their antihypertensive medications were stopped. Why do we think so differently when treating obesity?

The prevalence of obesity in the United States is over 40% and growing.^[14] We are fortunate to have new medications that on average lead to 15% or greater weight loss when combined with lifestyle modification. However, these medications are expensive and the limited insurance coverage currently available may not improve. From a patient experience perspective, it is distressing to have to discontinue treatments that have helped to achieve a healthier weight and then experience regain.

People need better access to evidence-based treatments for obesity, which include lifestyle interventions, anti-obesity medications, and bariatric procedures. Successful treatment of obesity should include a personalized, patient-centered approach that may require a combination of therapies, such as medications and surgery, for lasting weight control.

Jaime P. Almandoz, MD, MBA, has disclosed the following relevant financial relationships: Serve(d) as a consultant for Novo Nordisk; Eli Lilly and Company.

UNITED STATES ADULT DIABETES PREVALENCE RISES, BUT ONLY IN THE LEAN

More than 37 million people in the United States are estimated to have diabetes, accounting for 11.3% of the total population.^[15] A recent study by Adesoba and colleagues used data collected by the Behavioral Risk Factor Surveillance System,^[16] a program run by the US Centers for Disease Control and Prevention using telephone interviews in 2015-2020 with a total of 2,630,463 adult United States residents.^[17]

The study found that prevalence of diabetes among lean United States adults (body mass index [BMI] less than 25 kg/m²) significantly increased from 2015 to 2020, while diabetes prevalence stayed flat among people with overweight or obesity. In lean adults, the prevalence of diabetes rose from 4.5% in 2015 to 5.3% in 2020, a nearly 18% relative increase over the 6 years.

In contrast, among overweight and obese American adults the prevalence of diabetes was 14.0% in 2015 and 14.3% in 2020, a nonsignificant difference during the 6-year window, reported researchers from the Department of Health Policy and Management at the University of Arkansas for Medical Sciences in Little Rock in a recent report in Diabetes Care.^[17]

"We find it interesting that within the time period of our study only lean adults experienced an increase in diabetes prevalence. More studies are needed to elucidate what may be causing this," said Taiwo P. Adesoba, lead researcher on the study, in an interview.

A Signal for Broader Diabetes Screening?

The results suggest a need to better understand the increasing prevalence of diabetes among people with lower BMI and raise the issue of "whether we need to provide more resources to certain populations to ensure that everyone has access to regular diabetes screening," said Clare C. Brown, PhD, senior author of the report, who is also at the University of Arkansas for Medical Sciences.

Although the American Diabetes Association (ADA) now recommends routine serial diabetes screening for all asymptomatic adults starting when people reach 35 years old (and starting at a younger age in adults with risk factors including elevated weight), this standard has only been in place since 2022.^[18] Prior to that, dating back to before 2015, the ADA did not recommend routine serial screening for all asymptomatic adults until they were at least 45 years old.

And the US Preventive Services Task Force 2021 recommendations call for diabetes screening for asymptomatic people aged 35-70 years only if they have obesity or are overweight (BMI > 25 kg/m²).^[19]

Despite this, one possible explanation for the observed rise in diabetes prevalence among asymptomatic United States adults with normal weight is increased screening of these people. "Many clinicians follow the ADA screening guidelines. It is possible that the noted increased prevalence of lean diabetes is due, to some degree, to wider adoption of these screening recommendations, commented Dan V. Mihailescu, MD, interim chief of endocrinology at Cook County Health in Chicago, Illinois, who was not involved with the new report.

The authors of another recent study have also determined that using age, rather than weight, as the primary screening tool for diabetes would be the easiest, and most equitable, approach to capturing the most cases possible. The researchers, from the Northwestern University Feinberg School of Medicine, Chicago, Illinois, also call for screening from age 35 upwards for all United States adults.

"All major racial and ethnic minority groups develop diabetes at lower weights than White adults, and it's most pronounced for Asian Americans," said the lead author of that report, Matthew J. O'Brien, MD. Dr Mihailescu, too, supports the concept of more liberal screening. "Broader routine screening for diabetes has very little risk but could identify people with disease who may not present with typical risk factors. I hope that more primary care practitioners adopt the ADA screening guideline" and initiate screening in all adults once they reach 35 years old regardless of their BMI, he said.

Diabetes Type Remained Unconfirmed in Study

In the study by Adesoba and colleagues, respondents self-reported being diagnosed with diabetes. The authors acknowledged the data limitation of not being able to distinguish between type 1 and type 2 diabetes but maintained that "type 1 diabetes is unlikely to be the sole cause" of the increasing United States prevalence of lean diabetes.^[17]

They based this inference on the generally low prevalence of type 1 diabetes among all adults with diabetes -- a prevalence rate they estimated to be about 6% -- and the increasing prevalence of diabetes they found during the 6 years studied among lean adults who were at least 45 years old.

Mihailescu said the lack of more detailed information on diabetes type is a limitation. "Some of the cases reported as lean diabetes could have been latent autoimmune diabetes of adults (LADA)," he noted in an interview, adding that some studies have reported that 5% to 10% of adults initially diagnosed with type 2 diabetes actually have LADA. The numbers reported by Adesoba and colleagues "might represent a significant overestimation of the actual prevalence of lean diabetes," Mihailescu said. The study was also limited by its reliance on self-reports of weight and height, he added.

Subgroup Analyses: Diabetes Cases Rise in Certain Racial Groups, Women

Additional analyses in the report showed that among the 791,445 people with lean diabetes the adults who were at least 45 years old had a much higher diabetes prevalence -- 9.9% in 2020 -- compared to younger adults, who had a prevalence of just 1.3% in 2020.

However, the growth in prevalence from 2015 to 2020 seemed unaffected by age, with virtually identical odds ratios for prevalence in 2020 compared to 2015, which was 1.20 in those aged ≥ 45 years and 1.19 in younger adults.

A further subgroup analysis showed that people who self-identified as Black had the highest diabetes prevalence by race or ethnicity in every year included in the study, reaching a peak of 9.2% in 2020, with an odds ratio of 1.44 compared to 2015. Survey participants who identified as Hispanic had prevalence rates that rose from 5.5% in 2015 to 7.2% in 2020, with an odds ratio of 1.32. Among White survey participants the prevalence rate in 2020 was 4.4%, a significant odds ratio of 1.15 compared to 2015.

Diabetes prevalence also rose much more in women, who had a diabetes prevalence of 5.3% in 2020 and an odds ratio of 1.45 compared to 2015, bringing the prevalence rate in women much closer to the rate in men, which was 5.9% in 2020. Among men, the prevalence rate in 2020 did not significantly change from the rate in 2015 of 5.5%.

"We are still learning about lean diabetes, and we need to know more about the genetic and environmental mechanisms that influence insulin secretion, beta-cell mass and survival, and insulin resistance," noted Mihailescu. "Lean diabetes remains an understudied topic, and much more research is needed to better understand it."

The study received no funding. Adesoba, Brown, and Mihailescu have reported no relevant financial relationships.

DISPARITIES IN STATIN USE PERSIST IN HIGH-RISK AMERICANS

Atherosclerotic cardiovascular disease (ASCVD) is a major cause of mortality and morbidity around the world. Approximately 26 million people in the United States are impacted by this disease, which contributes to 2 million hospitalizations and 400,000 deaths annually.^[20] A new study, published in JAMA Cardiology, explored the use of primary prevention statins by race and ethnicity according to 10-year ASCVD risk. It also evaluated associations between several social determinants of health and statin use.^[21]

Using data from the National Health and Nutrition Examination Survey (NHANES), the researchers performed a serial, cross-sectional analysis of 3417 participants that they said represented 39.4 million United States adults after applying sampling weights for age, gender, and race and ethnicity. In the weighted sample, 62.2% were men. In terms of self-reported race and ethnicity, 4.2% were of Asian descent, 12.7% were Black, 10.1% were Hispanic, and 73% were White.

The researchers reported that the overall prevalence of statin use was 25.5%, and that it varied significantly between defined ethnic groups: 20% for Black participants, 15.4% for Hispanic participants, and 27.9% for White participants (P < .001). Statin use rates by Asian participants, at 25.5%, didn’t differ significantly from use by White participants.

Disparities in statin use in minority populations persist, regardless of insurance status and 10-year ASCVD risk. Those are among the findings of a study that sampled a national population database and has provided robust data and granular details on those disparities.

“We know that there are racial and ethnic disparities in the use of guideline-indicated statins after having established heart disease, but it was unknown if these disparities existed in the use of guideline-indicated statins for prevention of heart disease in those who just have risk factors,” lead author Joshua Jacobs, PharmD, a clinical pharmacist of cardiovascular medicine at University of Utah Intermountain Healthcare, said in written comments. “Additionally, race is included in the guideline-recommended risk factor calculation in an effort to reduce these disparities.”

Dr Jacobs and colleagues evaluated statins for use in primary prevention, building upon previous single-center or diabetes-only cohort studies. What makes their study different from previous studies evaluating disparities in statin use is its use of temporal trends or current 10-year predicted ASCVD risk categorization, he said.

Study participants completed a standardized questionnaire given by trained interviewers and went to mobile examination centers where physical, anthropomorphic, and laboratory measurements, including height, weight, low-density lipoprotein (LDL) cholesterol, and fasting blood glucose were collected. Pill bottle review also verified participants’ self-reported medication use.

The study noted that for primary prevention of ASCVD, the 2018 American College of Cardiology/American Heart Association Guideline recommends statins for, among other patient factors, elevated 10-year predicted ASCVD risk. The study divided ASCVD risk strata into three groups -- 5% to less than 7.5%, 7.5% to less than 20%, and more than 20% -- based on the 2018 ACC/AHA guideline and used pooled cohort equation to calculate 10-year ASCVD risk, which the guideline endorses.

Gaps Persist Despite ASCVD Risk

The analysis found no statistically significant difference within each ASCVD risk strata between the White and Asian groups. Although statin use increased proportionately across each higher risk group, the gap widened noticeably in the highest risk group (more than 20% 10-year risk) between White study participants, used as the reference at 37.6%, and Black study participants (23.8%; prevalence ratio [PR] 0.90; 95% CI: 0.82,0.98) and Hispanic study participants (23.9%; PR 0.90; 95% CI: 0.81, 0.99).

The study found that health insurance and access to routine health care were significantly associated with greater statin use in Black, Hispanic, and White participants; marital status and food insecurity were not. However, even when variables such as education, household income, and health insurance were applied, statin use was still significantly higher in White participants than in Black and Hispanic participants. For those with health insurance, statin use was 28.6% (95% CI: 25, 32), 21.1% (95% CI: 17.3, 25.4) and 19.9% (95% CI: 15.9, 24.5), respectively.

The study noted that the pooled cohort equation-guided approach to statins for primary prevention, which the 2018 ACC/AHA guideline endorsed, should promote greater use of statins among Black patients. “Equitable use of statin therapy for prevention of heart disease is needed for Black and Hispanic adults,” Dr Jacobs said. “Improvements in access to care, such as having a routine primary care clinician and health insurance, may decrease these health disparities.”

A goal of the study was to identify if disparities in statin use held up across different risk groups, senior author Ambarish Pandey, MD, said in an interview. Use of the NHANES data makes this study unique among analyses of statin use disparities, he said.

“A lot of the work that has been done previously has focused on secondary prevention among patients who have atherosclerotic cardiovascular disease or have focused on single-center or hospital-based cohorts and have not really focused on a national representative cohort like NHANES,” said Dr Pandey, of the UT Southwestern Medical Center, Dallas, Texas.

The next step is to do community-based participatory research focusing on different implementation strategies to increase the uptake of preventive statin use among Black and Hispanic communities, Dr Jacobs said.

Dr Jacobs has no relevant relationships to disclose. Dr Pandey disclosed relationships with Gilead Sciences, Applied Therapeutics, Myovista, Tricog Health, Eli Lilly, Cytokinetics, Rivus, Roche Diagnostics, Pieces Technologies, Palomarin, Emmi Solutions, and Axon.

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