Addition of linagliptin to metformin reduces prediabetes progression https://www.healio.com/news/endocrinology/20200106/addition-of...

January 06, 2020 2 min read

Addition of linagliptin to metformin reduces

prediabetes progression
Prediabetes was less likely to progress to type 2 diabetes among adults who took a combination of

linagliptin and metformin vs. metformin alone; the combination group was also more likely to achieve
normal glucose levels, according to findings published in Metabolism.

“It has been demonstrated that treatment of prediabetes reduces the risk of micro- and
macrovascular complications, as well as global mortality, highlighting the relevance of early

treatments for glucose abnormalities,” Rodolfo Guardado-Mendoza, MD, PhD, of the research
department at Hospital Regional de Alta Especialidad del Bajío and the department of medicine and

nutrition at the University of Guanajuato in Mexico, and colleagues wrote. “Evaluation of new
alternatives for patients with prediabetes is needed to generate scientific evidence about the safety

and e!cacy profile of these therapies to treat hyperglycemia at early stages.”

Guardado-Mendoza and colleagues examined how often type 2 diabetes developed or normal glycemic
levels were achieved using data from across 24 months for 144 adults with prediabetes in the
Prevention with Linagliptin, Lifestyle and Metformin (PRELLIM) study. The researchers randomly

assigned participants to a twice per day regimen of 2.5 mg linagliptin (Tradjenta, Boehringer
Ingelheim/Eli Lilly) and 850 mg metformin (n = 74; mean age, 48 years; 66.2% women) or a twice per

day regimen of 850 mg metformin (n = 70; mean age, 50 years; 55.7% women). The researchers
performed oral glucose tolerance tests and hyperglycemic clamps at 6-month intervals to examine

beta-cell function, serum glucose, insulin C-peptide and plasma glucagon levels. The researchers also
collected HbA1c data.

Participants assigned the combination experienced a 0.04% decrease in HbA1c at 24 months vs. a rise

of 0.42% among those assigned metformin alone (P < .01). The researchers wrote that “glucose levels
improved during the whole OGTT and during the entire follow-up, and these improvements were
significantly better” when comparing those taking the combination with those taking metformin

alone.

1 de 3 25/10/20 21:39
Addition of linagliptin to metformin reduces prediabetes progression https://www.healio.com/news/endocrinology/20200106/addition-of...

At 24 months, four participants assigned the combination had type 2 diabetes and 10 assigned
metformin alone had the condition (HR = 4; 95% CI, 1.24-13.04). In addition, at 24 months, 52.7% of

those assigned the combination achieved normal glycemic levels vs. 33.3% of those assigned
metformin alone. In fact, participants assigned the combination were 3.31 times more likely to achieve
normal glycemic levels than those assigned metformin alone (OR = 3.31; 95% CI, 1.54-7.09).

The researchers used an OGTT disposition index, which was a calculation combining acute insulin

response and fasting insulin, as the metric for beta-cell function, with higher scores indicating
superior function. Participants assigned the combination had scores of 2.41, 2.13 and 2.07 on the index

vs. 1.56, 1.6 and 1.72 for those assigned metformin alone at 6, 12 and 24 months, respectively (P < .05
at each timepoint). 

“Together, these improvements in pancreatic beta- and alpha-cell function with combined

treatments, like the one that we used in the linagliptin plus metformin group, highlights the role of
pancreatic islet cell function as an integrative functional unit to control glucose metabolism and
prevent type 2 diabetes, and perhaps due to this e#ect, the most e#ective therapies to prevent type 2

diabetes would be those with an important e#ect on pancreatic islet function combined with
lifestyle,” the researchers wrote. – by Phil Neu!er

Disclosures: The authors report no relevant financial disclosures.

PERSPECTIVE
Kevin M. Pantalone, DO, ECNU, FACE
Patients with prediabetes are not routinely treated with pharmacotherapy, and it can be challenging
for many patients to continue aggressive lifestyle modi=cations over the long-term even if such
interventions are instituted. A multifaceted approach to reduce the risk of developing type 2
diabetes, one that combines pharmacotherapy and lifestyle modi=cation, would appear to be a very
sound approach. The recent report by Guardado-Mendoza and colleagues demonstrated that an approach which
combines two medications — linagliptin plus metformin — in addition to lifestyle intervention improved glucose
metabolism and pancreatic beta-cell function and reduced the incidence of type 2 diabetes in subjects with
prediabetes as compared with metformin and lifestyle intervention alone.

While there are many potential interventions to reduce the risk of developing type 2 diabetes in patients with
prediabetes — and help many of them lose weight — =rst and foremost, we must do a better job of identifying
patients with prediabetes and initiating an intervention early in the disease process, when patients still have
signi=cant beta-cell function remaining, to really make a signi=cant impact on reducing the incidence of type 2
diabetes. In the coming years, it will be paramount that we do so in order to reduce the worldwide prevalence of
type 2 diabetes, which has been predicted to double by 2030.

Kevin M. Pantalone, DO, ECNU, FACE

Staff Endocrinologist
Director of Diabetes Initiatives
Department of Endocrinology
Cleveland Clinic

Disclosures: Pantalone reports he has received speaker honoraria from AstraZeneca, Merck and Novo Nordisk, research support from Merck and
Novo Nordisk and consulting honoraria from Bayer, Merck, Novo Nordisk and Sano=.

2 de 3 25/10/20 21:39
Addition of linagliptin to metformin reduces prediabetes progression https://www.healio.com/news/endocrinology/20200106/addition-of...

linagliptin metformin type 2 diabetes prediabetes

3 de 3 25/10/20 21:39