Pharmacological Management of Type 2 Diabetes

Overview

This Guidelines summary of Primary Care Diabetes Europe’s position statement, A disease state approach to the pharmacological management of Type 2 diabetes in primary care, outlines the treatment recommendations by cardiovascular/renal disease or risk factor. Please refer to the full guideline for a review on the current evidence for glycaemic efficacy, cardiovascular and renal risk, and side effects for a wide variety of therapies for type 2 diabetes.

All Patients with Type 2 Diabetes

• Side effects are major factors influencing treatment choice and medication adherence. Patients will have their personal needs and preferences. Shared decision making is an approach in which patients and clinicians work together and engage in a deliberate dialogue about reasonable treatment options
• As part of their first-line therapy, all patients with type 2 diabetes should be offered individualised and comprehensive lifestyle counselling including weight management, physical activity, dietary guidance, and smoking cessation
• To avoid therapeutic inertia, dual therapy may be considered at diabetes diagnosis in patients who are likely to benefit from better glycaemic control. The decision of whether to initiate dual therapy at diagnosis should consider individual patient characteristics and treatment goals
• All glycaemic and lifestyle goals should be co-developed and agreed to by the patient and physician. For patients who find it challenging to meet their glycaemic goals, therapeutic lifestyle modifications and adherence to these measures should be discussed at ongoing follow-up visits every three to six months. In addition to healthy lifestyle management, newly diagnosed patients with type 2 diabetes should also be treated with metformin as the first-line pharmacological therapy of choice
• If a dual therapy approach is used, in addition to achieving intensive glycaemic control very early in the disease trajectory, extra-glycaemic benefits such as prevention of cardiovascular disease, prevention of renal disease deterioration and weight loss could be gained
• If metformin monotherapy is chosen at diagnosis, patients should be monitored closely at ongoing follow-up visits every 3–6 months to avoid therapeutic inertia. For patients on dual therapy and not meeting treatment goals, additional intensification should be strongly considered to avoid therapeutic inertia.

Cardiovascular Risk Stratification in Patients With Type 2 Diabetes

• Patients with type 2 diabetes are considered to be at very high cardiovascular risk if they have any of the following:
  • history of cardiovascular disease (CVD)
  • multiple uncontrolled CVD risk factors, including hypertension, hyperlipidaemia, obesity, smoking and/or physical inactivity
  • estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m²
  • albuminuria
  • age at diagnosis <40 years
• All other patients with type 2 diabetes are considered to be at high cardiovascular risk.

Treatment Recommendations

Atherosclerotic Cardiovascular Disease

• Consider initiating metformin + sodium-glucose co-transporter-2 inhibitors (SGLT2i)/glucagon-like peptide-1 receptor agonist (GLP-1RA) rather than stepwise
• Metformin as first-line therapy
• SGLT2i or GLP-1RA with proven cardiovascular benefit as second-line therapy
• Use basal insulin with caution when other options have failed, and glycaemic targets are not met
• When deciding on the most appropriate and effective antihyperglyaemic medication to add after or with metformin, it is important to consider the presence of other diabetes-associated comorbidities. The presence of atherosclerotic cardiovascular disease (ASCVD) in people with type 2 diabetes strongly advocates choosing a glucose-lowering drug that controls and prevents the worsening of ASCVD, hospitalisation for heart failure (HF), renal disease and mortality
• Therapy in patients at increased risk of stroke should also be focused on lowering blood pressure, which has been shown to dramatically lower risk
• Patients and HCPs should also discuss the considerable inter-individual variation in magnitude of effect on HbA_1c and weight loss in patients treated with GLP‑1RAs, and continued treatment with these therapies should be evaluated after six months
• Importantly, insulin should only be used in patients with type 2 diabetes and ASCVD when other options have been attempted and co-developed glycaemic goals have not been met, except if the patient presents with acute hyperglycaemic osmotic symptoms, diabetic ketoacidosis, or hyperglycaemic hyperosmolar non-ketotic coma. However, these presentations are not routinely managed in primary care.

Heart Failure

• Consider initiating metformin + SGLT2i rather than stepwise
• Metformin as first-line therapy
• SGLT2i as second-line therapy
• Avoid pioglitazone and saxagliptin and use basal insulin with caution
• For those with HF, patients and HCPs should carefully weigh the benefits of stricter glycaemic control against the risks of worsening HF, with reduced insulin intensification given serious consideration.

Chronic Kidney Disease

• Consider initiating metformin + SGLT2i rather than stepwise, according to the approved restrictions of dose and indications by eGFR
• Metformin as first-line therapy if eGFR>30 ml/min/1.73 m²
• SGLT2i as second-line therapy in patients with >45 ml/min/1.73 m², even when well-controlled on metformin alone
• GLP-1RA as third-line therapy or if previous treatments are not tolerated, followed by dipeptidyl peptidase-4 inhibitor (DPP-4i)
• Reduce dose of glinides and reduce dose or discontinue sulfonylureas (SUs) if eGFR <45 ml/min/1.73 m² to reduce the risk of hypoglycaemia
• Consult prescribing instructions for specific agents for dosing instructions based on eGFR.

High Cardiovascular Risk

• Overall, it is the role of the primary care physician to view the patient as a whole. Patients with type 2 diabetes at high cardiovascular risk should also be assessed and treated for non-diabetes-related risk factors such as smoking cessation, dyslipidaemia and hypertension
• Consider initiating metformin + SGLT2i/GLP-1RA/DPP-4i rather than stepwise
• Metformin as first-line therapy
• SGLT2i or GLP-1RA or DPP-4i as second-line therapy where cost is not prohibitive. Of these, SGLT2i or GLP-1RA with proven cardiovascular benefit is preferred
• Newer-generation SUs or glinides when drug cost must be minimised
• Pioglitazone in patients with non-alcoholic fatty liver disease and where insulin resistance predominates
• Basal insulin when other therapies have been explored and glycaemic targets are not met
• Full basal—bolus insulin therapy only as a last resort
• For patients who remain above target after initiation of basal insulin, insulin/GLP-1RA combination therapies may be an attractive alternative to full basal–bolus therapy, leading to reduced weight gain compared to insulin therapy at equivalent or better glycaemic control.

Obesity

• Weight loss between 5% and 10% of starting body weight has been shown to be beneficial and should be a healthy lifestyle goal for most patients with type 2 diabetes
• Consider initiating metformin + GLP-1RA/SGLT2i rather than stepwise
• Metformin as first-line therapy
• GLP-1RA or SGLT2i as second-line therapy
• Where possible, avoid treatments that cause weight gain, including most SUs, glinides, pioglitazone, and insulin
• If basal insulin is required, consider fixed-ratio insulin/GLP-1RA combinations.

Elderly/Frail Patients

• Quality of life should be a priority focus for patients who are elderly/frail. Stringent glycaemic targets are unlikely to be appropriate in this population due to the reduced life expectancy in which to accrue microvascular benefits, and because of the increased risk of hypoglycaemia
• Avoid stringent glycaemic targets that increase risk of hypoglycaemia
• Metformin as first-line therapy if tolerated and not contraindicated
• DPP-4i is a safe and easy to use option
• Assess adherence and avoid multiple daily injectable medications when possible.