Diabetes: Treatment for

Diabetes: Treatment for Type 2 Outline

• Overview

  • Brief history of diabetes treatments

  • Sites of action of treatments

  • Drug classes

  • Additional treatment options

  • Combinations therapy

  • Focus on diet, exercise, and surgery

  • Summary and take-home message

Latest News

• Announcement of a significant shake-up in type 2 diabetes care expected to roll out by August 20, 2025

  • Millions to gain earlier access to new treatments

  • Associated with NICE's re-evaluation of clinical pathways per the 10-Year Health Plan for the NHS

Current NICE Guidelines

• Rescue Therapy

  • In cases of symptomatic hyperglycemia, consider:

  • Insulin therapy

  • Sulfonylurea therapy

  • Importance of reviewing treatment once blood glucose control is achieved

• First-Line Treatment

  • Assess:

  • HbA1c levels

  • Cardiovascular Risk

  • Kidney Function

  • Treatment pathways based on cardiovascular disease (CVD) risk

  • Not at high risk for CVD:

    • Offer Metformin, DPP-4 inhibitors (gliptins), or Pioglitazone

    • Metformin Extended Release (MR) or Sulfonylurea can also be considered

    • SGLT2 inhibitors indicated if cardiovascular benefits are demonstrated

  • High risk for CVD:

    • Offer Metformin or Metformin MR when necessary

    • SGLT2 inhibitors also an option if Metformin tolerability is confirmed

  • NICE Technology Appraisals Recommendations

  • Canagliflozin, Dapagliflozin, Empagliflozin, Ertugliflozin for specific patients

  • SGLT2 inhibitors as monotherapy if Metformin is contraindicated

  • Established Atherosclerotic CVD includes conditions such as:

  • Coronary heart disease

  • Previous myocardial infarction

  • Stable angina

  • Cerebrovascular disease

  • Peripheral arterial disease

Pharmacological Management

• Early Treatment Approach

  • Emphasis on lifestyle changes (diet/exercise) first, followed by Metformin

  • If Metformin intolerable, progress to rescue therapies:

  • Sulfonylurea

  • Insulin

  • Possible consideration of bariatric surgery

Drug Classes and Actions

• Biguanides

  • Example: Metformin

  • Mechanism: Decreases hepatic glucose production

  • Notes: Mainstay for Type 2 diabetes, especially in obese patients, does not stimulate insulin release; caution in renal insufficiency

• Sulfonylureas

  • Example: Glyburide, Glipizide, Glimepiride

  • Mechanism: Insulin secretagogues that stimulate pancreatic insulin secretion

  • Use: Effective in non-obese Type 2 diabetics but may cause weight gain

• Meglitinides

  • Example: Repaglinide, Nateglinide

  • Mechanism: Stimulates pancreatic insulin secretion

  • Use: Ingested before meals; rapid onset, short duration; risk of hypoglycemia

• Thiazolidinediones (TZDs)

  • Example: Pioglitazone

  • Mechanism: Sensitizes peripheral tissues to insulin

  • Cautions: Weight gain, heart failure risks, history of bladder cancer

• Alpha-glucosidase Inhibitors

  • Example: Acarbose

  • Mechanism: Delays carbohydrate absorption in the intestines

  • Not recommended currently by NICE

• SGLT2 Inhibitors

  • Mechanism: Increases urinary glucose excretion by inhibiting glucose reabsorption in kidneys

  • Common drugs: Canagliflozin, Dapagliflozin, Empagliflozin, Ertugliflozin

  • Side Effects: Increased risk of urinary tract and yeast infections

• GLP-1 Agonists (Incretin Mimetics)

  • Actions Include:

  • Enhancing glucose-dependent insulin secretion

  • Inhibiting glucagon secretion

  • Slowing gastric emptying

  • Increasing satiety

  • Examples: Liraglutide, Exenatide

  • Mechanism: Mimics natural incretin hormones to regulate glucose homeostasis, also overlooks appetite control

• DPP-4 Inhibitors

  • Example: Sitagliptin

  • Mechanism: Prevents breakdown of GLP-1 thus increasing insulin secretion and decreasing glucagon secretion

  • Rare side effects include pancreatitis and liver toxicity

• Amylin Mimetics

  • Example: Pramlintide

  • Mechanism: Slows gastric emptying, decreases post-meal glucagon level

  • Side Effects: Gastrointestinal discomfort, nausea/vomiting

Dietary Guidelines for Type 2 Diabetes Management

• Focus on Individualized Nutritional Advice

  • High-fiber, low-glycemic-index foods including fruits, vegetables, whole grains, and pulses

  • Low-fat dairy and oily fish consumption

  • Monitoring and reduction of saturated and trans fats

  • For overweight adults, a target weight loss of 5% to 10% should be discussed

• Emphasize Personalization of Dietary Advice

  • Integrate dietary plans with overall diabetes management, including increased physical activity

  • Reduce hypoglycemia risk for those on insulin or insulin secretagogues

Exercise Recommendations for Type 2 Diabetes

• Regular exercise impacts health positively:

  • Decreases HbA1c levels

  • Reduces cardiovascular morbidity

  • Increases life expectancy

  • Lowers risk of gestational diabetes and development of type 2 diabetes

Additional Treatments and Surgical Options

• Bariatric Surgery

  • Types include:

  • Roux-en-Y Gastric Bypass: Effective in weight reduction and diabetes remission

  • Adjustable Gastric Banding

  • Vertical Sleeve Gastrectomy

  • Biliopancreatic Diversion with Duodenal Switch

Combination Therapies for Type 2 Diabetes

• Effective Treatment Combinations:

  • Metformin with Thiazolidinediones

  • Metformin combined with DPP-4 inhibitors

  • SGLT2 inhibitors paired with other oral antidiabetic agents

  • GLP-1 agents combined with Metformin and Pioglitazone

  • Insulin therapy used alongside Metformin or Sulfonylureas

Conclusion - Take-Home Messages

• Integrated approach required for management of Type 2 Diabetes in adults

• Importance of latest NICE guidelines including emerging drugs like Tirzepatide for future treatments

• Emphasis on personalized treatment pathways, effective interventions combining lifestyle changes and pharmacotherapy