What is the appropriate management for a 58-year-old male with uncontrolled type 2 diabetes mellitus (T2DM), hyperglycemia, impaired renal function, hyperlipidemia, hypertension, intermittent claudication, and neuropathic symptoms, currently taking metformin (Metformin) and hydrochlorothiazide (Hydrochlorothiazide)?

From the Guidelines

The patient's current treatment plan for type 2 diabetes mellitus should be intensified with the addition of a second agent, such as an SGLT-2 inhibitor or a GLP-1 receptor agonist, to achieve better glycemic control and reduce the risk of cardiovascular complications, as recommended by the most recent guidelines 1. The patient's hemoglobin A1c level is 10.1%, indicating poor glycemic control. An appropriate HbA1c goal for this 58-year-old patient with type 2 diabetes and multiple complications would be around 7-7.5%. This less stringent target is appropriate given his cardiovascular disease risk factors, peripheral vascular disease, and diabetic neuropathy.

• Diet and exercise remain crucial components of his treatment plan despite failing on maximum metformin.
• Even with medication, lifestyle modifications can improve insulin sensitivity and help with weight management.
• His BMI of 29 kg/m2 indicates he is overweight, and losing weight would benefit his glycemic control and cardiovascular health.
• Metformin works by decreasing hepatic glucose production, increasing peripheral glucose uptake, and improving insulin sensitivity without causing hypoglycemia or weight gain.
• Other oral antidiabetic agents include sulfonylureas (stimulate insulin secretion), DPP-4 inhibitors (increase incretin levels), SGLT-2 inhibitors (block glucose reabsorption in kidneys), thiazolidinediones (improve insulin sensitivity), and alpha-glucosidase inhibitors (delay carbohydrate absorption).
• His blood pressure of 155/94 mmHg is not adequately controlled, as the target for diabetic patients is <140/90 mmHg.
• His kidney function evaluation is incomplete; a 24-hour urine collection for protein and creatinine clearance would provide better assessment.
• His lipid profile is suboptimal with elevated LDL and triglycerides and low HDL.
• He should have annual comprehensive eye exams with dilation to monitor his diabetic retinopathy.
• For his neuropathic pain, medications like pregabalin, gabapentin, duloxetine, or amitriptyline could help.
• His night sweats may be due to nocturnal hypoglycemia or autonomic neuropathy.
• His impotence likely stems from diabetic autonomic neuropathy, vascular disease, or medication side effects.
• Additional pharmacological interventions should include intensifying his diabetes treatment with a second agent (SGLT-2 inhibitor or GLP-1 receptor agonist), adding a statin for dyslipidemia, and optimizing his antihypertensive regimen, as supported by recent studies 1.

From the FDA Drug Label

Metformin hydrochloride tablets are contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 Initiation of metformin hydrochloride tablets is not recommended in patients with eGFR between 30 to 45 mL/min/1. 73 m 2. Obtain an eGFR at least annually in all patients taking metformin hydrochloride tablets. In patients taking metformin hydrochloride tablets whose eGFR falls below 45 mL/min/1. 73 m 2, assess the benefit and risk of continuing therapy.

The patient has impaired renal function, and the eGFR level is not specified. However, given the patient's impaired renal function, caution is advised when using metformin.

• The patient's renal function should be assessed before continuing metformin therapy.
• The benefit and risk of continuing metformin therapy should be evaluated, considering the patient's impaired renal function and other comorbidities.
• Alternative treatment options may need to be considered if the patient's eGFR is below 45 mL/min/1.73 m^2 or if the risk of lactic acidosis is deemed too high 2.
• Close monitoring of the patient's renal function, blood sugar levels, and overall health is necessary to minimize the risk of adverse effects 2.

From the Research

Management of Uncontrolled Type 2 Diabetes Mellitus

The management of a 58-year-old male with uncontrolled type 2 diabetes mellitus (T2DM), hyperglycemia, impaired renal function, hyperlipidemia, hypertension, intermittent claudication, and neuropathic symptoms, currently taking metformin and hydrochlorothiazide, requires a comprehensive approach.

• Medication Management:
  • Metformin is a commonly used first-line treatment for T2DM, but its use may be associated with gastrointestinal disturbances and increased plasma homocysteine levels, which can accelerate vascular disease 3.
  • The addition of a second-line agent such as a sulfonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitor, or thiazolidinedione may be considered to improve glycemic control 4, 5.
  • However, the choice of second-line agent should be individualized based on the patient's renal function, risk of hypoglycemia, and other comorbidities.
• Glycemic Control:
  • The goal of treatment is to achieve a hemoglobin A1c (HbA1c) level of less than 7% to minimize the risk of microvascular and macrovascular complications 6, 7.
  • In addition to HbA1c, postprandial glucose and fasting plasma glucose levels should also be monitored to assess glycemic control 7.
• Cardiovascular Risk Reduction:
  • The patient's history of hypertension, hyperlipidemia, and intermittent claudication increases his cardiovascular risk, and therefore, aggressive management of these risk factors is necessary.
  • The use of medications such as statins, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers may be considered to reduce cardiovascular risk.
• Neuropathic Symptoms:
  • The patient's neuropathic symptoms should be managed with medications such as gabapentin or pregabalin, and lifestyle modifications such as regular exercise and foot care.
  • The patient's renal function should be closely monitored when using these medications, as they may be nephrotoxic.

Considerations for Treatment

• Insulin Therapy:
  • Insulin therapy may be considered if the patient's HbA1c level remains elevated despite optimal doses of oral medications 6.
  • However, insulin therapy is associated with an increased risk of hypoglycemia and weight gain.
• Glucagon-Like Peptide-1 Receptor Agonists:
  • Glucagon-like peptide-1 receptor agonists such as exenatide or liraglutide may be considered as an alternative to insulin therapy 6.
  • These medications have been shown to improve glycemic control and reduce cardiovascular risk, but may be associated with gastrointestinal side effects.