Botanical compound boosts blood sugar control in prediabetes, early T2D

The novel plant-based polyphenol-rich compound, TOTUM-63, helps keep the lid on fasting plasma glucose (FPG) and other measures of glucose dysregulation in people with prediabetes and early type 2 diabetes (T2D), according to the pivotal phase II/III REVERSE-IT study.

REVERSE-IT achieved its primary outcome of FPG after 6 months of treatment, with TOTUM-63 at 5 g, regardless of when divided into 3 (TID) or 2 (BID) daily doses, having yielded significantly greater reductions in FPG compared with placebo (mean change from baseline, –1.9 and –4.2 mg/dl, respectively, vs 3.9 mg/dl; p<0.01 and p<0.001, respectively), reported one of the study authors Dr André Marette from Quebec Heart and Lung Institute, Laval University in Quebec City, Quebec, Canada. [EASD 2024, abstract 698]

In a subgroup analysis, the effect of TOTUM-63 on FPG was significant among participants with prediabetes and only numerically greater relative to placebo among participants with T2D. Marette, however, pointed out that the T2D subpopulation comprised a small number of participants (between 38 and 45), which might have contributed to the nonsignificant result.

In terms of other outcomes, TOTUM-63 was also associated with reductions in HbA1c (–0.08 percent with TID and –0.15 percent with BID vs 0.03 percent with placebo; p=0.06 and p<0.01, respectively), body weight (–1.2 kg with TID and –1.3 kg with BID vs –0.5 kg with placebo; p<0.05 for both comparisons), and lipid profile such as triglycerides and total cholesterol. Additionally, the 2h-glycaemic response to a glucose overload was better with TOTUM-63 than with placebo (–9.8 mg/dl with TID and –13.9 mg/dL with BID vs 7.94 mg/dL with placebo; p=0.08 and p<0.05, respectively).

Marette noted that at 6 months, progression from prediabetes to T2D occurred in significantly fewer participants in the TOTUM-63 TID and BID groups than in the placebo group (19.9 percent and 15.8 percent vs 27.5 percent, respectively; p<0.05 for both comparisons).

TOTUM-63 was well tolerated, with compliance being more than 96 percent across the treatment groups, he added.

TOTUM-63 is a polyphenol-rich plant cocktail that consists of artichoke, chrysanthellum, olive leaf, bilberry, and black pepper extracts. The compound is said to target the pathophysiological mechanisms of T2D, including (1) inflammation (blood high-sensitivity C-reactive protein and fibrinogen), which is involved in the development of insulin resistance; (2) certain key gastrointestinal hormones (GIP and PYY), which contribute to the regulation of metabolism and satiety; and (3) metabolic response after meals. [https://tinyurl.com/2y64edkq]

Already, the compound has been shown to have beneficial effects on metabolic and anthropometric parameters in preclinical studies and in a 6-month pilot clinical study involving 51 individuals with prediabetes or early stage newly diagnosed T2D. [Int J Mol Sci 2023;24:3652; Nutr Metab Cardiovasc Dis 2022;32:1797-1807; Int J Obes 2021;45:2016-2027; Diabetes Obes Metab 2022;24:2331-2340]

“REVERSE-IT is one of the largest and most ambitious studies in the world with nondrug approaches to early dysglycemia, from prediabetes to the early stages of T2D. The results of this study represent a significant breakthrough for these people with glycaemic impairment and confirm the data obtained in … [the pilot] study,” stated one of the study authors Prof Jean-Marie Bard, president of the French Nutrition Society Scientific Committee, in a news release.

“Many healthcare professionals will be able to provide a solution for their patients and change their clinical practices, which until now have been limited to lifestyle recommendations alone,” Bard added.

For the study, Marette and Bard, along with the rest of their team, recruited 636 adults from 52 sites across seven European countries. The participants were between 18 and 70 years of age and had prediabetes (n=501, 78.8 percent) or newly diagnosed T2D (n=135, 21.2 percent) that did not require immediate glucose-lowering treatment. Their baseline BMI was between 25 and 40 kg/m².

The participants were randomly assigned to receive TOTUM-63 5 g divided into either three daily administrations (n=212, mean age 57.0 years, 53.8 percent female) or two daily administrations (n=214, mean age 55.9 years, 60.3 percent female) or placebo divided into three daily doses (n=210, mean age 56.8 years, 61.4 percent female). There was no significant change in food habits or in physical activity in the 3 months before the randomization.