Early Data for GLP-1 Pill; FAERS Tirzepatide Reports; AI Diabetes Voice Screening

Studies presented at the European Association for the Study of Diabetes (EASD) annual meeting in Madrid included early data for oral amycretin, safety data for tirzepatide (Mounjaro, Zepbound), and voice screening for diabetes.

Early Data for Oral Amycretin

Twelve weeks of daily oral treatment with an investigational compound yielded significant weight loss in a phase I, first-in-human study.

The compound was oral amycretin — an amylin and GLP-1 receptor co-agonist — said Agnes Gasiorek, PhD, MSc Pharm, of Novo Nordisk in Måløv, Denmark. It’s the first long-acting compound to target both hormones in a single molecule, she said.

Average reduction in body weight from baseline in adults with a BMI between 25 and 39.9 without diabetes was 10.4% with a once-daily 50-mg dose and 13.1% with two 50-mg doses taken together.

Compared with placebo, those on one 50-mg dose and two 50-mg doses lost 9.2% (95% CI -12 to -6.5%) and 11.8% (95% CI -14.6 to -9%) more weight. Weight loss still had not plateaued by the end of the 12 weeks. “It really is remarkable for an orally delivered biologic,” said Gasiorek.

The study involved a few parts testing different ascending dose strategies. The efficacy results stemmed from part C, which included 16 participants who titrated up to a maximum of 50 mg, 16 who titrated up to a maximum of two 50-mg doses, and 12 on placebo. Participants were on the maximum dose only for the last 2 weeks of the trial. Average age was around 39, most were male, and average baseline BMI was 31.

Most adverse events were mild or moderate and gastrointestinal-related, including nausea, vomiting, and decreased appetite. Two serious adverse events occurred in other parts of the study, which included acute cholecystitis and diabetic ketoacidosis, Gasiorek said.

“The magnitude of weight loss observed following only 12 weeks … supports continued evaluation in larger and longer studies to fully assess the safety and efficacy of amycretin,” Gasiorek said.

Real-World Safety Data for Tirzepatide

There was a disproportionate number of several adverse event reports with tirzepatide but its safety profile was generally similar to other GLP-1 receptor agonists, according to a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS).

Among 20,409 reports associated with tirzepatide related to 1,432 adverse events, there was a significantly higher reporting odds ratio (ROR) for the following with tirzepatide:

• Nausea: ROR 4.01 (95% CI 3.85-4.19)
• Pancreato-biliary disorders (i.e., pancreatitis): ROR 3.63 (95% CI 3.15-4.19)
• Diabetic retinopathy: ROR 4.14 (95% CI 2.34-7.30)
• Medullary thyroid cancer: ROR 13.67 (95% CI 4.35-42.96)

Over a third (38%) of adverse events were in regards to administration site and procedural complications. This included things like injection site injury (ROR 52.78, 95% CI 45.75-60.89) and incorrect dose administered (ROR 43.66, 95% CI 42.33–45.01).

A total of 17% of all adverse events included gastrointestinal disorders and 12% involved nutrition and metabolism disorders like “starvation” (ROR 41.57, 95% CI 27.22-63.48).

Tirzepatide is a first-in-class injectable featuring a combination of a glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (GLP-1/GIP) agonist. Compared with GLP-1 receptor agonists as a class, tirzepatide had generally a similar risk for gastrointestinal events and medullary thyroid cancer. It had better overall gastrointestinal tolerability than semaglutide (Ozempic, Wegovy), but worse than lixisenatide and albiglutide.

There was also a lower rate of diabetic retinopathy and most pancreato-biliary adverse events with tirzepatide compared with other GLP-1s.

The findings were “reassuring,” said Irene Caruso, MD, PhD, of the University of Bari Aldo Moro in Italy during a presentation. “Despite the unprecedented glucose and weight-loss lowering efficacy of tirzepatide, it comes with a similar — if not improved — safety profile as GLP-1 receptor agonists.”

But Caruso advised caution when extrapolating the results since there was a low number of certain events like thyroid cancer.

The findings were also published in the Journal of Endocrinological Investigation.

Diabetes Voice Screening?

An artificial intelligence (AI) algorithm was able to detect diabetes from a short recording of people’s voices with about 70% accuracy. It also displayed 96% and 93% agreement with the questionnaire-based American Diabetes Association risk score in women and men, respectively.

In a key subgroup analysis, the algorithm performed even better in men and women with hypertension and women 60 and older.

“Most current methods of screening for type 2 diabetes require a lot of time and are invasive, lab-based, and costly,” said Abir Elbeji, PhD student, of the Luxembourg Institute of Health in Strassen. “Combining AI with voice technology has the potential to make testing more accessible by removing these obstacles. This study is the first step towards using voice analysis as a first-line, highly scalable type 2 diabetes screening strategy.”

Researchers included data from 607 U.S. participants in the Colive Voice study, about half with type 2 diabetes and half without. The researchers collected 25-second voice recordings of participants reading article 25 of the Universal Declaration of Human Rights and analyzed a wide array of vocal features like changes in pitches, intensity, and tone to pinpoint differences between individuals with and without diabetes.

Two advanced techniques were used — one that captured up to 6,000 detailed vocal characteristics plus a deep-learning approach that focused on a refined set of 1,024 key features.

Women and men with type 2 diabetes tended to be slightly older (average ages for females were 49.5 vs 40 years; for males, average ages were 47.6 vs 41.6 years) and were more likely to have obesity (average BMI for females was 35.8 vs 28; for males, it was 32.8 vs 26.6) than those without type 2 diabetes.

“While our findings are promising, further research and validation are necessary before the approach has the potential to become a first-line diabetes screening strategy and help reduce the number of people with undiagnosed type 2 diabetes. Our next steps are to specifically target early-stage type 2 diabetes cases and pre-diabetes,” added co-author Guy Fagherazzi, PhD, also of the Luxembourg Institute of Health, in a statement.

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