“The use of glucagon-like peptide-1 receptor agonists—or GLP-1RAs—has increased dramatically, but recommendations suggest their discontinuation before pregnancy because there’s not enough information about their safety for unborn babies,” said lead author Jacqueline Maya, MD, a pediatric endocrinologist at Mass General Brigham for Children. “We sought to assess how such discontinuation affects weight gain and outcomes during pregnancy.”

For the study, the team analyzed electronic health records for 1,792 pregnancies delivered within the Mass General Brigham healthcare system between 2016–2025, primarily among women with obesity. Each woman with a GLP-1RA prescription within three years before and up to 90 days after conception was matched to three similar pregnancies where the mother did not use GLP-1RAs.

Individuals who stopped GLP-1RAs before or in early pregnancy gained an average of 7.2 pounds more weight during pregnancy than those who did not use the weight loss drugs. The GLP-1RA group also had a 32% higher risk of excess weight gain (gaining more than recommended), a 30% higher risk of diabetes during pregnancy, a 29% higher risk of hypertensive disorders during pregnancy, and a 34% higher risk of preterm delivery. There were no differences in risk of high or low birth weight, birth length, or Cesarean delivery.

“Additional studies are needed on the balance of pre-pregnancy benefits of GLP-1s with the risks associated with interrupting them for pregnancy,” said senior author Camille E. Powe, MD, a Mass General Brigham endocrinologist and co-director of the Diabetes in Pregnancy Program at Massachusetts General Hospital. “We need to do more research to find ways to help manage weight gain and reduce risks during pregnancy when stopping GLP-1 medications.”

Authorship: In addition to Maya and Powe, Mass General Brigham authors include Deepti Pant, Yiran Fu, Kaitlyn James, Carolina Batlle, Sarah Hsu, Diana C. Soria-Contreras, Lydia Shook, Christopher Mow, Marie-France Hivert, and Tanayott Thaweethai.

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The study was carried out by researchers at the University of Eastern Finland, and the results were published in Clinical Epidemiology.

Patients belonging to each trajectory group were followed up for another eight years for diabetes complications. During the follow-up, 13% of all patients developed microvascular complications, 21% developed macrovascular complications and 20% of patients deceased. The risk of microvascular complications was 2.9 times higher and the risk of macrovascular complications 2.5 times higher among patients with an increasing BMI compared to those with a stable BMI. Micro- and macrovascular complications of diabetes can include, for example, retinopathy, nephropathy and neuropathy, as well as cardiovascular diseases.

“These results underscore the significance of continuous BMI monitoring and weight management in patients with type 2 diabetes. Tailored treatments and support with lifestyle changes are crucial for efficiently preventing weight gain and reducing the risk of diabetes complications,” says Doctoral Researcher Zhiting Wang of the University of Eastern Finland.

The study was carried out in North Karelia, Finland, using electronic health records from both primary and specialised health care. The study included a total of 889 adults with newly diagnosed type 2 diabetes in 2011 or 2012. The participants were grouped based on individual BMI trajectories from the diagnosis until 2014. Risks for microvascular complications, macrovascular complications, any diabetes complications and all-cause mortality from 2015 to 2022 across BMI trajectory groups were estimated.

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They published their findings on Dec. 19, 2023 in BMJ Nutrition Prevention & Health.

As background, the authors noted, “Women seem to have more difficulty quitting smoking than men. This is particularly concerning as smoking puts women at a higher risk of developing smoking-associated diseases.”

Findings from a previously published trial indicated that dulaglutide significantly reduced weight gain in those of both genders who quit smoking. But the prior analysis did not determine whether weight loss was specific to gender.

In this new analysis, the investigators re-analysed the data for gender differences in weight loss or gain during 12 weeks after smoking cessation.

They included 255 adults in the analysis. All had been daily smokers (155 women, 100 men).

All subjects had received weekly dulaglutide (1.5 mg) or placebo (0.9% sodium chloride). In addition, all received standard smoking cessation care including varenicline 2 mg/day plus behavioral counselling, which lasted for 12 weeks.

The investigators defined “substantial weight gain” as an increase of more than 6% in body weight.

The investigators found that women were more likely than men to put on substantial weight during the timeframe of the study.

Dulaglutide treatment was associated with a significantly lower risk of substantial weight gain among the women.

Substantial weight gain among subjects in the placebo treatment cohorts (not receiving dulaglutide) was much more frequent in women than in men, 24% for women vs 5% for men.

Notably, substantial weight gain in women treated with dulaglutide was significantly less common than those who did not get the drug, 1% (1 out of 83) vs 24% (17 out of 72) (p<0.001).

Similar statistically significant weight gain effects did not appear among the men, 0% (0/44) in the dulaglutide-treated group vs 5% (3/56) in the placebo-treated group.

“Dulaglutide reduced post-cessation weight gain in both genders and was very effective in preventing substantial weight gain, which seems to be a   specific observation in females,” the authors concluded.

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That chewing food well makes a healthy eating habit is age-old wisdom. Slow eating and thorough chewing help prevent obesity and weight gain — a view popularized a century back and tested afterward in sporadic scientific studies. Typically, the chewing process reportedly enhances the energy expenditure associated with the metabolism of food and increases intestinal motility — all summing up to an increased heat generation in the body after food intake, known as diet-induced thermogenesis (DIT). However, how prolonged chewing induces DIT in the body remains unclear. Recently, Dr. Yuka Hamada and Professor Naoyuki Hayashi from Waseda University, Japan, have published a study that provides a causal link between chewing and DIT. The study has been published in the journal Scientific Reports.

DIT, also known as the thermic effect of food consumption, increases energy expenditure above the basal fasting level — a factor known to prevent weight gain. Earlier, the team found that slow eating and thorough chewing not only increased DIT but also enhanced blood circulation in the splanchnic region of the abdomen. Although these studies linked chewing-induced-DIT with increased digestion and absorption-related activity in the abdomen, they left scopes for further exploring a few crucial points. Hayashi explains, “We were unsure whether the size of the food bolus that entered the digestive tract contributed to the increase in DIT observed after slow eating. Also, do oral stimuli generated during prolonged chewing of food play any role in increasing DIT? To define slow chewing as an effective and scientific weight management strategy, we needed to look deeper into these aspects.”

To find the answers, the researchers designed their new study to exclude the effect of the food bolus by involving liquid food. The entire study included three trials conducted on different days. In the control trial, they asked the volunteers to swallow 20-mL liquid test food normally every 30 seconds. In the second trial, the volunteers kept the same test food in their mouth for 30 seconds without chewing, thereby allowing prolonged tasting before swallowing. Lastly, in the third trial they studied the effect of both chewing and tasting; the volunteers chewed the 20-mL test food for 30 seconds at a frequency of once per second and then swallowed it. The variables such as hunger and fullness, gas-exchange variables, DIT, and splanchnic circulation were duly measured before and after the test-drink consumption.

The results of this well-designed study turned up to be quite insightful. There was no difference in hunger and fullness scores among the trials. However, as Hayashi describes, “We found DIT or energy production increased after consuming a meal, and it increased with the duration of each taste stimulation and the duration of chewing. This means irrespective of the influence of the food bolus, oral stimuli, corresponding to the duration of tasting food in the mouth and the duration of chewing, increased DIT.” Gas exchange and protein oxidation too increased with the duration of taste stimulation and chewing, and so did blood flow in the splanchnic celiac artery. As this artery supplies blood to the digestive organs, the motility of the upper gastrointestinal tract also increased responding to oral stimuli during chewing.

The study highlighted that chewing well, by increasing energy expenditure, can indeed help prevent obesity and metabolic syndrome. Hayashi concludes, “While the difference in energy expenditure per meal is small, the cumulative effect gathered during multiple meals, taken over every day and 365 days a year, is substantial.”

Backed by robust science, slow eating and thorough chewing could be the latest recommendations for integration into our weight management efforts.

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