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Healthy behaviour interventions should be initiated in people newly diagnosed with type 2 diabetes.• In people with type 2 diabetes with A1C <1.5% above the person's individualized target, antihyperglycemic pharmacotherapy should be added if glycemic targets are not achieved within 3 months of initiating healthy behaviour interventions.• In people with type 2 diabetes with A1C ≥1.5% above target, antihyperglycemic agents should be initiated concomitantly with healthy behaviour interventions, and consideration could be given to initiating combination therapy with 2 agents.• Insulin should be initiated immediately in individuals with metabolic decompensation and/or symptomatic hyperglycemia.• In the absence of metabolic decompensation, metformin should be the initial agent of choice in people with newly diagnosed type 2 diabetes, unless contraindicated.• Dose adjustments and/or additional agents should be instituted to achieve target A1C within 3 to 6 months. Choice of second-line antihyperglycemic agents should be made based on individual patient characteristics, patient preferences, any contraindications to the drug, glucose-lowering efficacy, risk of hypoglycemia, affordability/access, effect on body weight and other factors.• In people with clinical cardiovascular (CV) disease in whom A1C targets are not achieved with existing pharmacotherapy, an antihyperglycemic agent with demonstrated CV outcome benefit should be added to antihyperglycemic therapy to reduce CV risk.• In people without clinical CV disease in whom A1C target is not achieved with current therapy, if affordability and access are not barriers, people with type 2 diabetes and their providers who are concerned about hypoglycemia and weight gain may prefer an incretin agent (DPP-4 inhibitor or GLP-1 receptor agonist) and/or an SGLT2 inhibitor to other agents as they improve glycemic control with a low risk of hypoglycemia and weight gain.• In people receiving an antihyperglycemic regimen containing insulin, in whom glycemic targets are not achieved, the addition of a GLP-1 receptor agonist, DPP-4 inhibitor or SGLT2 inhibitor may be considered before adding or intensifying prandial insulin therapy to improve glycemic control with less weight gain and comparable or lower hypoglycemia risk.

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Aims:To compare the efficacy and safety of once-daily prandial lixisenatide with placebo in type 2 diabetes mellitus (T2DM) insufficiently controlled by pioglitazone ± metformin. Methods:This randomized, double-blind study included a 24-week main treatment period and a ≥52-week variable extension period.Patients were randomized 2 : 1 to receive lixisenatide 20 μg once daily or placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) at week 24. Results:In total, 484 patients were randomized: 323 to lixisenatide; 161 to placebo. After 24 weeks, lixisenatide once daily significantly improved HbA1c (−0.56% vs. placebo; p < 0.0001) and increased the proportion of patients achieving HbA1c <7% compared with placebo (52.3% vs. 26.4%, respectively; p < 0.0001) and significantly improved fasting plasma glucose (−0.84 mmol/l vs. placebo; p < 0.0001). There was a small decrease in body weight with lixisenatide once daily and a small increase with placebo, with no statistically significant difference between the two groups. Overall, lixisenatide once daily was well tolerated, with a similar proportion of treatment-emergent adverse events (TEAEs) and serious TEAEs between groups (lixisenatide: 72.4% and 2.5%; placebo: 72.7% and 1.9%). Symptomatic hypoglycaemia rates were also relatively low in both groups (lixisenatide 3.4% and placebo 1.2%), with no severe episodes. Lixisenatide continued to be efficacious and well tolerated during the variable extension period. Conclusions:Lixisenatide once daily significantly improved glycaemic control with a low risk of hypoglycaemia, and was well tolerated over 24 weeks and during the long-term, double-blind extension period in patients with T2DM insufficiently controlled on pioglitazone ± metformin.

The chronic hyperglycemia of diabetes is associated with significant longterm microvascular and macrovascular complications. A fasting plasma glucose level of 7.0 mmol/L, a 2-hour plasma glucose value in a 75 g oral glucose tolerance test of 11.1 mmol/L or a glycated hemoglobin (A1C) value of 6.5% can predict the development of retinopathy. This permits the diagnosis of diabetes to be made on the basis of each of these parameters. The term "prediabetes" refers to impaired fasting glucose, impaired glucose tolerance or an A1C of 6.0% to 6.4%, each of which places individuals at high risk of developing diabetes and its complications.