Headlines in type 2 diabetes this year featured new approvals, continued access issues for GLP-1 agonists, guidance on surgery timing with that widely used class of drugs, and emerging risk factors for the metabolic disease.
FDA Approvals Expand Options
New type 2 diabetes approvals in 2023 included a label update for oral semaglutide (Rybelsus), allowing the GLP-1 receptor agonist to be used as a first-line option in adults, as well as new options for pediatric patients.
Two SGLT2 inhibitor-containing treatments — once-daily empagliflozin (Jardiance) and empagliflozin/metformin hydrochloride (Synjardy) — were approved for patients ages 10 and up, marking the first oral options for children since metformin was approved for pediatric use in 2000. While not approved in the pediatric setting, another SGLT2 inhibitor — dapagliflozin (Farxiga) — showed HbA1c-lowering benefits for kids in the phase III T2NOW trial this year.
Advances in management of the disease have been critical, especially in the face of a growing burden of diabetes. A report this year projected a doubling in worldwide diabetes cases in the coming decades, with 1.3 billion people expected to have the disease by 2050.
GLP-1 Agonist Access, Surgery Timing, and Label Updates
Unprecedented demand and manufacturing issues for injectable GLP-1 drugs semaglutide (Ozempic, Wegovy for obesity) and the dual GLP-1/GIP agonist tirzepatide (Mounjaro) left many patients with type 2 diabetes struggling to maintain access to these agents throughout the year.
In fact, the FDA still lists both drugs as currently being in shortage, prompting compounded forms of the popular drugs. But in May, the agency warned that certain compounded forms are using semaglutide sodium and semaglutide acetate, which are not the same active ingredient as the approved versions. The agency also said it had received reports of adverse events associated with these unapproved formulations.
As the use of GLP-1 agonists became more and more widespread, a new surgical safety signal emerged, leading to new American Society of Anesthesiologists (ASA) guidance. Given that the drugs can delay gastric emptying, ASA advised that patients on a once-weekly injectable form of a GLP-1 agent hold their medication at least a week prior to elective surgery due to the risk for aspiration.
Also, the FDA this year updated the labeling for both semaglutide and tirzepatide to include postmarketing reports of ileus, or blocked intestines.
Other Diabetes Risk Factors Emerge
Several studies this year broadened the scope of what we know to be linked with type 2 diabetes development.
One particular analysis found that some women had a significantly higher incidence of type 2 diabetes if they had greater daily exposure to phthalates — an endocrine-disrupting class of chemicals commonly used as plasticizers, such as for vinyl flooring, food packaging, and even clothing. Over 6 years of follow-up, each doubling of the concentration of five different types of phthalates was linked with up to a 63% higher incidence.
Another study found that people who consumed the highest daily amount of nitrites in their food had a 27% greater diabetes risk compared with those who consumed the least. The French research group that reported the findings also noted that the highest consumption levels of nitrites originating from additives — particularly sodium nitrite e250, often used as a color fixer — carried a 54% higher diabetes risk.
Pediatric Group Warns Against Keto Diet in Kids
More and more people have turned to keto and other types of low-carbohydrate diets to curb their risk for diabetes. However, the American Academy of Pediatrics (AAP) recently issued a warning that youngsters should avoid this fad. In the AAP’s Committee on Nutrition’s clinical report, it was noted that restricting carbohydrates in young people with or at-risk for diabetes can increase the risk for growth disorders, bone issues, nutritional deficiencies, nutritional ketosis, and disordered eating habits. These types of diets also are not recommended for any youth with type 1 diabetes.
Instead, the committee advised that youth should opt for a more balanced diet to curb diabetes risk, reducing their ultra-processed carbohydrate intake and increasing fiber consumption. Kids should also consume fewer sugary beverages and more whole fruits and vegetables, the AAP said.
Research Continues to Move the Needle
A randomized trial published this year suggested that even patients with type 2 diabetes can benefit from using a fully closed-loop insulin delivery system (also known as an artificial pancreas). In other insulin news, the phase IIIa ONWARDS 1 trial presented at this year’s American Diabetes Association (ADA) annual meeting showed a greater average reduction in HbA1c with icodec compared with glargine U100 for type 2 diabetes patients, with an estimated between-group difference of -0.19% at 52 weeks (95% CI -0.36 to -0.03).
And new tirzepatide data released from the SURPASS-6 trial — part of the clinical program that underpins the first-in-class GLP-1/GIP agonist’s diabetes indication — showed that patients with poorly controlled disease who added basal insulin experienced a 2.1% average drop in HbA1c by week 52 compared with a 1.1% drop in those who added three-times-daily insulin lispro instead.
Finally, novel investigational GLP-1 agents turned up positive mid-stage data at ADA as well. Orforglipron, an oral nonpeptide GLP-1 receptor agonist, led to a significantly lower reduction in HbA1c versus placebo by week 26, with drops of 2.1% and 0.43%, respectively. Likewise, the triple-hormone receptor agonist retatrutide outperformed placebo at reducing HbA1c at all doses tested, and most were also better than 1.5 mg dulaglutide (Trulicity). The highest retatrutide dose (12 mg) yielded a 2.02% reduction in HbA1c by week 24.
Other type 2 diabetes-related news for 2023 included: