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Management of Type 2 Diabetes

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Step 1: Initial Assessment and Lifestyle Intervention

Diagnosis: Confirm diagnosis of Type 2 Diabetes with HbA1c ≥ 6.5% (48 mmol/mol) or fasting plasma glucose ≥ 7.0 mmol/L.
Lifestyle Intervention:
- Dietary modifications focusing on balanced nutrition, weight management, and carbohydrate control.
- Encourage regular physical activity (at least 150 minutes of moderate-intensity exercise per week).
- Behavioral support, including smoking cessation and alcohol moderation.
Monitoring: Regular monitoring of blood glucose levels, HbA1c, blood pressure, and lipid profile.

Step 2: Initiation of First-Line Pharmacotherapy

Metformin:
- Start with Metformin monotherapy unless contraindicated.
- Titrate dose gradually to minimize gastrointestinal side effects.
Alternative First-Line Options: If Metformin is contraindicated or not tolerated:
- DPP-4 inhibitors (e.g., Sitagliptin, Linagliptin).
- SGLT2 inhibitors (e.g., Empagliflozin, Dapagliflozin), especially if cardiovascular or renal benefits are a priority.
- GLP-1 receptor agonists (e.g., Liraglutide) may be considered in certain cases, especially with obesity.

Step 3: Intensification of Therapy

Add a Second Oral Agent or GLP-1 Agonist: If HbA1c targets are not met after 3 months on monotherapy.
- Add an SGLT2 inhibitor, DPP-4 inhibitor, or sulfonylurea based on patient profile and comorbidities.
- Consider adding a GLP-1 receptor agonist if weight loss is desired or if the patient has cardiovascular disease.
Dual Therapy: Combine Metformin with an additional agent as per individual needs:
- Metformin + SGLT2 inhibitor for cardiovascular benefits and renal protection.
- Metformin + DPP-4 inhibitor for those who need a well-tolerated combination.
- Metformin + Sulfonylurea for cost-effective options, but monitor for hypoglycemia.

Step 4: Consideration of Insulin Therapy

Basal Insulin: Initiate basal insulin if HbA1c targets are not achieved with dual or triple oral therapy.
- Start with a long-acting insulin, such as Insulin Glargine or Insulin Degludec.
- Adjust the dose based on fasting blood glucose levels.
GLP-1 Receptor Agonist + Basal Insulin: Consider combination therapy to reduce the insulin dose and minimize weight gain.
Prandial Insulin: Introduce prandial (mealtime) insulin if needed to control postprandial glucose levels.

Step 5: Ongoing Monitoring and Adjustment

Regular Follow-Up: Monitor HbA1c every 3-6 months, adjust medications as needed to achieve and maintain target HbA1c.
Assess for Complications: Regularly screen for diabetic complications (retinopathy, nephropathy, neuropathy) and manage accordingly.
Lifestyle Reinforcement: Continue to reinforce the importance of lifestyle modifications, including diet and exercise.
Patient Education: Provide ongoing education on self-management, recognizing hypoglycemia, and the importance of adherence to treatment.

Conclusion

Management of Type 2 Diabetes requires a patient-centered approach, with regular monitoring, lifestyle intervention, and stepwise pharmacotherapy. Treatment should be individualized based on patient preferences, comorbidities, and the risk of complications. Regular follow-up is essential to adjust therapy and achieve optimal glycemic control.

Medication Class	Common Drugs	Mechanism of Action	Common Side Effects	Notes
Biguanides	Metformin	Reduces hepatic glucose production and improves insulin sensitivity.	Gastrointestinal disturbances (e.g., nausea, diarrhea), lactic acidosis (rare)	First-line therapy for type 2 diabetes; contraindicated in renal impairment.
Sulfonylureas	Gliclazide, Glibenclamide, Glipizide	Stimulates pancreatic beta cells to release insulin.	Hypoglycemia, weight gain	Often used as second-line therapy; risk of hypoglycemia.
DPP-4 Inhibitors	Sitagliptin, Saxagliptin, Linagliptin	Inhibits DPP-4 enzyme, increasing incretin levels and stimulating insulin release.	Nasopharyngitis, headache, pancreatitis (rare)	Weight-neutral; generally well-tolerated.
SGLT2 Inhibitors	Empagliflozin, Dapagliflozin, Canagliflozin	Inhibits SGLT2 in the kidneys, reducing glucose reabsorption and increasing urinary glucose excretion.	Urinary tract infections, genital infections, dehydration, ketoacidosis (rare)	Benefits in cardiovascular risk reduction; avoid in severe renal impairment.
Thiazolidinediones (TZDs)	Pioglitazone, Rosiglitazone	Increases insulin sensitivity by activating PPAR-gamma receptors.	Weight gain, fluid retention, risk of heart failure, fractures	Used with caution due to cardiovascular risks; avoid in heart failure.
Alpha-Glucosidase Inhibitors	Acarbose, Miglitol	Delays carbohydrate absorption in the intestines by inhibiting alpha-glucosidase.	Flatulence, diarrhea, abdominal pain	Less commonly used; taken with meals to reduce postprandial hyperglycemia.
Meglitinides	Repaglinide, Nateglinide	Stimulates rapid insulin secretion from the pancreas in response to meals.	Hypoglycemia, weight gain	Short-acting; taken before meals to reduce postprandial glucose levels.
Bile Acid Sequestrants	Colesevelam	Binds bile acids in the intestine, which reduces glucose production and improves glycemic control.	Constipation, nausea, bloating	Primarily used for cholesterol management; may also lower blood glucose.

Long-acting insulin preparations are essential in the management of diabetes mellitus, particularly for maintaining baseline insulin levels and achieving better glycaemic control. These insulins are designed to be released slowly over a prolonged period, typically 24 hours or more, providing a stable insulin level throughout the day and night. In the UK, several long-acting insulin preparations are available for use.

Available Long-Acting Insulin Preparations

Insulin Type	Brand Names	Onset	Peak	Duration	Notes
Insulin Glargine	Lantus, Abasaglar, Toujeo	1-2 hours	Minimal peak	24 hours or more	Lantus and Abasaglar are typically given once daily at the same time each day. Toujeo is a more concentrated form of insulin glargine, providing a longer duration of action and less variability in blood sugar levels.
Insulin Detemir	Levemir	1-2 hours	6-8 hours	Up to 24 hours	Levemir is often dosed once or twice daily, depending on the patient’s needs. It may have a slightly shorter duration of action compared to insulin glargine, necessitating twice-daily dosing in some cases.
Insulin Degludec	Tresiba	1-2 hours	Minimal peak	42 hours	Tresiba offers the longest duration of action among long-acting insulins, up to 42 hours. It provides flexibility in dosing time, allowing patients to inject at different times each day without losing efficacy.

Clinical Considerations

When selecting a long-acting insulin for a patient, several factors should be considered:

Patient's Lifestyle: The choice of insulin may depend on the patient’s daily routine and flexibility in dosing schedules. For example, Tresiba may be preferred for patients who need flexibility in dosing times.
Glycemic Control: Insulin glargine and insulin degludec are often preferred for patients requiring stable, around-the-clock insulin coverage with minimal peaks.
Dosing Frequency: Insulin detemir may require twice-daily dosing in some patients, which could influence the choice of insulin.
Cost and Availability: The availability of certain brands and the cost to the patient or healthcare system may also impact the choice of insulin.

Conclusion

Long-acting insulin preparations play a crucial role in the management of diabetes, providing basal insulin coverage to help maintain blood glucose levels within the target range. The choice of insulin should be individualized based on the patient's needs, lifestyle, and response to therapy. Regular follow-up and adjustment of the insulin regimen are essential to achieving optimal glycemic control.

PLEASE NOTE LEGAL ADVICE: The contents are under continuing development and improvements and may contain errors of omission or fact. Feedback vital and always welcome at drokane at gmail.com. This is not to be used for the assessment, diagnosis or management of patients. It should not be regarded as medical advice. It is only for educational purposes. Please adhere to your local protocols. If you are unwell please seek healthcare advice from your doctor. This does not replace senior or specialist advice. If you do not accept this then please do not use the website. If you need medical advice, please consult a doctor or other appropriate medical professional. If you are a medical professional and you need advice then speak to your senior or colleagues.

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