medwireNews: Upfront treatment with medications that target the underlying pathophysiology of prediabetes may slow patients’ progression to type 2 diabetes, report researchers.
During an average 32.09 months of follow-up, none of the highest-risk patients, who were given the most intensive treatment including a glucagon-like peptide (GLP)-1 receptor agonist, progressed to diabetes, compared with 11% of patients with moderate or high risk for diabetes progression who received only lifestyle advice.
The Successful Treatment of Prediabetes (STOP DIABETES) study is published in The Lancet Diabetes & Endocrinology, along with a linked commentary, in which Robert Ryder (City Hospital, Birmingham, UK) notes that “[m]any would consider intervention with three pharmaceutical agents, one of which is an injectable, to be excessive in this population.”
But he stresses that “the complications of type 2 diabetes can be devastating and anything that can be done to avoid diabetes and therefore its complications is worthy of consideration.”
The researchers also note the additional costs of pharmacologic treatment at this early stage of diabetes, but observe that “regimens using inexpensive agents (metformin and pioglitazone) provide substantial benefit and expensive agents are nearing generic availability.”
Their study was not a randomized trial; the 200 patients in the lifestyle advice group comprised those who refused pharmacologic treatment. John Armato (Providence Little Company of Mary Cardiometabolic Center, Torrance, California, USA) and co-researchers therefore stress the need for “[a] larger, multicentre study with a diverse, multiethnic population.”
The other patients were allocated treatment according to the presence and severity of defects in their glycemic response, insulin sensitivity, or insulin secretion, determined with an oral glucose tolerance test. The 81 thought to be at the highest risk (two severe defects or one severe plus two moderate defects) received pioglitazone, metformin, lifestyle therapy, and a GLP-1 receptor agonist, and the 141 with fewer/milder defects received the same but without the GLP-1 receptor agonist.
The reduced risk for progression to diabetes remained significant after accounting for variables including age, BMI, and baseline insulin sensitivity and secretion, both for patients receiving the most intensive treatment and for those given intermediate treatment (4.1% of whom progressed), relative to the lifestyle therapy group. The corresponding numbers needed to treat to prevent one person progressing to diabetes were 24 and 41.
Moreover, 77% and 52% of people receiving intensive and intermediate therapy, respectively, regained normal glucose tolerance, compared with 39% of those receiving lifestyle advice.
“Our study suggests that clinicians might want to reconsider their approach to prediabetes on the basis of the pathophysiology of the disease in individual patients and should not simply rely on fasting plasma glucose and [glycated hemoglobin] concentrations,” say Armato and team.
Pharmacologic treatment resulted in improved insulin sensitivity and beta-cell function. Only patients taking a GLP-1 receptor agonist lost a significant amount of weight (1.8 kg vs lifestyle advice). Among all patients analyzed together, beta-cell function was the only significant independent predictor of progression to diabetes, with each one unit increase in disposition index associated with a 99% risk reduction.
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