What are the clinical presentations of newly diagnosed type 2 diabetes mellitus (T2DM)?

From the Guidelines

The first presentation of type 2 diabetes should be managed with a comprehensive approach, starting with metformin 500mg once daily and lifestyle modifications, as this approach has been shown to improve outcomes and reduce morbidity and mortality 1. The management of type 2 diabetes requires a multifaceted approach that includes lifestyle modifications and medication.

• Lifestyle modifications should include a balanced diet with reduced carbohydrates, regular physical activity (aim for 150 minutes of moderate exercise weekly), and weight loss of 5-10% if overweight.
• Medication should start with metformin 500mg once daily with meals, gradually increasing to 1000mg twice daily as tolerated over 2-4 weeks to minimize gastrointestinal side effects.
• Monitor blood glucose regularly, with a target fasting glucose of 80-130 mg/dL and HbA1c below 7%.
• If metformin alone is insufficient after 3 months, add a second-line agent such as a SGLT-2 inhibitor (like empagliflozin 10mg daily) or a GLP-1 receptor agonist (like semaglutide, starting at 0.25mg weekly and titrating up), as recommended by recent guidelines 1.
• These medications are particularly beneficial for patients with cardiovascular disease or risk factors, and have been shown to reduce morbidity and mortality in patients with type 2 diabetes 1.
• Schedule follow-up appointments every 3 months initially to assess treatment efficacy and adjust therapy as needed. This approach addresses the underlying insulin resistance and relative insulin deficiency characteristic of type 2 diabetes, while the combination of medication and lifestyle changes helps prevent complications and disease progression.
• It is also important to note that type 2 diabetes frequently goes undiagnosed for many years, and simple tests to detect preclinical disease are readily available 1.
• Effective interventions that prevent progression from prediabetes to diabetes are also available, and should be considered in patients at high risk of developing type 2 diabetes 1.

From the Research

First Presentation of Type 2 Diabetes

• The first presentation of type 2 diabetes typically involves the initiation of metformin therapy as soon as the patient is diagnosed, as it has been shown to improve long-term clinical outcomes compared with initial management with diet alone, without increasing the risk of developing hypoglycemia or weight gain 2.
• International guidelines recommend metformin as the first-line treatment for patients with type 2 diabetes, with additional therapy dependent on multiple patient-specific factors, including cardiovascular risks, risk of hypoglycemia, metabolic changes, and cost 3.
• The extended-release formulation of metformin (met XR) has the potential to overcome the limitations of the immediate-release formulation, including gastrointestinal adverse effects, and is considered a convenient dose regimen 2.

Treatment Options

• For patients who are on metformin-sulfonylurea dual therapy, the addition of a dipeptidyl peptidase-4 inhibitor (DPP4i) is considered a preferred third-line medication, with the lowest risks of mortality and severe hypoglycemia, and posing no increased risk for cardiovascular disease events when compared to insulin and thiazolidinediones 4.
• DPP-4 inhibitors may be considered as a clinically stable choice for second-line therapy after completing maximally tolerated doses of metformin, despite the higher efficacious characteristics of sulfonylureas in lowering HbA1c, due to their reported hypoglycemic effects 3.
• Sulfonylureas are considered better than DPP-4 inhibitors for treatment in patients with cardiovascular disease history and hypoglycemia 3.

Safety and Efficacy

• A systematic review and meta-analysis found that DPP-4 inhibitors compared to sulfonylureas produced a non-significant difference in HbA1c% change, whereas a significant decrease in the rate of hypoglycemic events was observed in favor of DPP-4 inhibitors 5.
• The review also found that body weight decreased by 2.2 kg with DPP-4 inhibitors, compared with sulfonylureas, and that there were insufficient data to assess a difference in the risk for cardiovascular events 5.