In the Journals

HbA1c, insulin use predict real-world response to GLP-1 receptor agonists in type 2 diabetes

A patient’s response to GLP-1 receptor agonist therapy in type 2 diabetes depends on several pretreatment characteristics, including baseline HbA1c, diabetes duration, age and use of insulin therapy, according to a real-world analysis published in Current Medical Research and Opinion.

Didac Mauricio

“In a real-world cohort of obese patients with poorly controlled type 2 diabetes, the addition of GLP-1 receptor agonists was effective in reducing weight and glycemia after 6 to 12 months to a degree similarly seen in clinical trials,” Didac Mauricio, MD, PhD, director of the department of endocrinology and nutrition at Hospital de la Santa Creu i Sant Pau in Barcelona, Spain, told Endocrine Today. “However, the probability of achieving a clinically meaningful glycemic response (reduction 1% in HbA1c) varied depending on the patient’s pretreatment characteristics. In the study, patients were frequently treated with insulin (40%), and the median diabetes duration was 7 years, suggesting that GLP-1 receptor agonists were initiated in patients with advanced disease vs. patients in early stages, when the latter is associated with better glycemic response.”

In a retrospective study, Mauricio and colleagues analyzed data from 4,242 patients with type 2 diabetes who initiated GLP-1 receptor agonist therapy between 2007 and 2014 in primary health care centers in Catalonia, Spain (47.9% men; mean age, 59 years; median diabetes duration, 7.3 years; mean HbA1c, 8.82%; mean BMI, 37.5 kg/m²). Researchers evaluated changes in HbA1c and body weight at 6 to 12 months, as well as factors independently associated with achieving a reduction of at least 1% in HbA1c.

Researchers found that mean HbA1c for the cohort fell from 8.8% to 7.7% at 6 to 12 months after initiating therapy, with 47.2% of patients experiencing an HbA1c reduction of at least 1%. Patients lost a mean of 3.6 kg, with 60% of patients experiencing a reduction in both body weight and HbA1c. Women experienced greater weight loss vs. men (mean, –4.1 vs. –3.1; P = .007), according to researchers.

Independent determinants of a 1% HbA1c reduction were baseline HbA1c, age, diabetes duration and background insulin therapy, according to researchers.

In results stratified by GLP-1 receptor agonist type, researchers found that the reduction in weight or HbA1c and the proportion of patients achieving a HbA1c reduction of at least 1% was larger among adults prescribed liraglutide (Victoza, Novo Nordisk) vs. exenatide (Byetta/Bydureon, AstraZeneca) and lixisenatide (Adlyxin, Sanofi).

“The results showed that this class of antidiabetic drugs works in different groups of patients with type 2 diabetes, but the response varied depending on the characteristics of the patient and the prescribed drug,” Mauricio said. “Identifying and prospectively differentiating profiles of subjects that predict the odds of response to GLP-1 receptor agonists should help physicians when making medication choices in complex patients. For example, long diabetes duration and prior insulin therapy seemed to decrease the probabilities of achieving an HbA1c reduction of at least 1% in our study. Conversely, a high pretreatment HbA1c value, older age or use of liraglutide were predictors of meaningful glycemic response.”

Mauricio said the findings speak to a need to conduct large observational studies in real-world settings to characterize the clinical interindividual differences in therapeutic response to antidiabetic drugs.

“Variables such as medication adherence or the effect of adverse events on treatment discontinuation need to be specifically studied to assess how they impact the clinical results,” Mauricio said. – by Regina Schaffer

For more information:

Didac Mauricio, MD, PhD, can be reached at the Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, Sant Quinti, 89, 08041, Barcelona, Spain; email: didacmauricio@gmail.com.

Disclosures: Novo Nordisk provided some funding for this study. Mauricio reports he has received advisory or speaking fees from AstraZeneca, Ascensia, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, MSD, Novartis, Novo Nordisk and Sanofi, and has received research grants to his institution from AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, MSD, Novartis, Novo Nordisk and Sanofi. Please see the study for all other authors’ relevant financial disclosures.

A patient’s response to GLP-1 receptor agonist therapy in type 2 diabetes depends on several pretreatment characteristics, including baseline HbA1c, diabetes duration, age and use of insulin therapy, according to a real-world analysis published in Current Medical Research and Opinion.

Didac Mauricio

“In a real-world cohort of obese patients with poorly controlled type 2 diabetes, the addition of GLP-1 receptor agonists was effective in reducing weight and glycemia after 6 to 12 months to a degree similarly seen in clinical trials,” Didac Mauricio, MD, PhD, director of the department of endocrinology and nutrition at Hospital de la Santa Creu i Sant Pau in Barcelona, Spain, told Endocrine Today. “However, the probability of achieving a clinically meaningful glycemic response (reduction 1% in HbA1c) varied depending on the patient’s pretreatment characteristics. In the study, patients were frequently treated with insulin (40%), and the median diabetes duration was 7 years, suggesting that GLP-1 receptor agonists were initiated in patients with advanced disease vs. patients in early stages, when the latter is associated with better glycemic response.”

In a retrospective study, Mauricio and colleagues analyzed data from 4,242 patients with type 2 diabetes who initiated GLP-1 receptor agonist therapy between 2007 and 2014 in primary health care centers in Catalonia, Spain (47.9% men; mean age, 59 years; median diabetes duration, 7.3 years; mean HbA1c, 8.82%; mean BMI, 37.5 kg/m²). Researchers evaluated changes in HbA1c and body weight at 6 to 12 months, as well as factors independently associated with achieving a reduction of at least 1% in HbA1c.

Researchers found that mean HbA1c for the cohort fell from 8.8% to 7.7% at 6 to 12 months after initiating therapy, with 47.2% of patients experiencing an HbA1c reduction of at least 1%. Patients lost a mean of 3.6 kg, with 60% of patients experiencing a reduction in both body weight and HbA1c. Women experienced greater weight loss vs. men (mean, –4.1 vs. –3.1; P = .007), according to researchers.

Independent determinants of a 1% HbA1c reduction were baseline HbA1c, age, diabetes duration and background insulin therapy, according to researchers.

In results stratified by GLP-1 receptor agonist type, researchers found that the reduction in weight or HbA1c and the proportion of patients achieving a HbA1c reduction of at least 1% was larger among adults prescribed liraglutide (Victoza, Novo Nordisk) vs. exenatide (Byetta/Bydureon, AstraZeneca) and lixisenatide (Adlyxin, Sanofi).

“The results showed that this class of antidiabetic drugs works in different groups of patients with type 2 diabetes, but the response varied depending on the characteristics of the patient and the prescribed drug,” Mauricio said. “Identifying and prospectively differentiating profiles of subjects that predict the odds of response to GLP-1 receptor agonists should help physicians when making medication choices in complex patients. For example, long diabetes duration and prior insulin therapy seemed to decrease the probabilities of achieving an HbA1c reduction of at least 1% in our study. Conversely, a high pretreatment HbA1c value, older age or use of liraglutide were predictors of meaningful glycemic response.”

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Mauricio said the findings speak to a need to conduct large observational studies in real-world settings to characterize the clinical interindividual differences in therapeutic response to antidiabetic drugs.

“Variables such as medication adherence or the effect of adverse events on treatment discontinuation need to be specifically studied to assess how they impact the clinical results,” Mauricio said. – by Regina Schaffer

For more information:

Didac Mauricio, MD, PhD, can be reached at the Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, Sant Quinti, 89, 08041, Barcelona, Spain; email: didacmauricio@gmail.com.

Disclosures: Novo Nordisk provided some funding for this study. Mauricio reports he has received advisory or speaking fees from AstraZeneca, Ascensia, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, MSD, Novartis, Novo Nordisk and Sanofi, and has received research grants to his institution from AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, MSD, Novartis, Novo Nordisk and Sanofi. Please see the study for all other authors’ relevant financial disclosures.