ENDO 11 DIABETES THERAPEUTICS

RISK FACTORS FOR TYPE 2 DIABETES

• Age 40 years or older

• First degree relative with type 2 diabetes

• African, Arab, Asian, Hispanic, Indigenous, South Asian

• Overweight

• Drugs associated with diabetes

  • Glucocorticoids

  • Atypical antipsychotics

  • Statins

  • Highly active antiretroviral therapy

  • Anti-rejection drugs

LIFESTYLE INTERVENTIONS

• Nutrition decreases A1C by 1-2%

• Metformin decreases A1C by 1-1.5%

  • Sulfonylureas, repaglinide, GLP1 RA

• TZDs decrease A1C by 1%

• SGLT2i decrease A1C by 0.5-0.8%

• Exercise decreases A1C by 0.5-0.7%

• DPP4I decreases A1C by 0.5-0.7%

1. Screening and Diagnosis for Diabetes

Diabetes is diagnosed using blood tests that measure sugar levels. The main ones are:

• Fasting Plasma Glucose (FPG) ≥ 7.0 mmol/L → Check sugar after fasting for 8+ hours

• A1c ≥ 6.5% → Measures the average sugar over 3 months

• 2-hour Plasma Glucose in OGTT ≥ 11.1 mmol/L → After drinking a sugary drink, if blood sugar is too high

• Random Plasma Glucose ≥ 11.1 mmol/L + symptoms → If high sugar is found randomly in a person with symptoms like excessive thirst, urination, and fatigue

Screening is important because diabetes can be silent for years. We screen:

• Everyone over 40 every 3 years

• Earlier if high risk (obesity, family history, high blood pressure, history of gestational diabetes, etc.)

2. Importance of Lifestyle Changes in Managing Diabetes

Think of diabetes like a leaky faucet. Medications can help, but if you don’t tighten the faucet (lifestyle changes), the water (blood sugar) will keep rising.

• Diet: Eating fewer processed carbs/sugars and more fiber, protein, and healthy fats helps slow down sugar spikes.

• Exercise: Increases insulin sensitivity, so the body can use sugar more efficiently.

• Weight Loss (if applicable): Losing even 5-10% of body weight can improve blood sugar control.

Lifestyle changes can sometimes delay or even reverse diabetes (in early stages).

3. Choosing the Right Medications for Type 2 Diabetes

Medications are chosen based on the patient’s specific needs:

💡 Deprescribing: If a patient achieves remission or has side effects, we can stop some meds (e.g., sulfonylureas first).

4. Similarities & Differences Between Antihyperglycemic Agents

• Similarities: All lower blood sugar but in different ways.

• Differences: Some help with weight loss (SGLT2i, GLP-1 RAs), some cause hypoglycemia (insulin, sulfonylureas), and some protect the heart/kidneys (SGLT2i, GLP-1 RAs).

5. Diabetes is Progressive, but Remission is Possible

• Type 2 diabetes gets worse over time because beta cells wear out and make less insulin.

• Remission (A1c < 6.5% without meds) is possible early on with weight loss and aggressive lifestyle changes (especially with significant weight loss from bariatric surgery).

6. Target A1c for Different Patients

A1c goals are personalized:

7. Lowering Blood Sugar ≠ Always Beneficial

Too much sugar lowering can be dangerous if it causes hypoglycemia, especially in older adults. Some trials showed aggressive control did not reduce death rates (e.g., ACCORD trial).

8. Evidence from Outcome Trials

Some meds do more than just lower sugar. Big trials (like EMPA-REG, LEADER) show that:

• SGLT2 inhibitors & GLP-1 RAs protect the heart and kidneys.

• Sulfonylureas & insulin lower sugar but don’t have heart/kidney benefits.

9. Blood Sugar Monitoring – How Often?

Depends on medications:

10. Hypoglycemia (Low Blood Sugar) – What to Know

• Definition: Blood sugar < 4.0 mmol/L

  • u can literally die after being in a coma —> hypoglycemia is not epic

• Symptoms:

  • Shaky, sweaty, dizzy, hungry, fast heartbeat, confusion

  • Nocturnal = nightmare, restless sleep, sweating, morning headache

** Beta blockers might mask symptoms of hypoglycemia EXCEPT SWEATING

—> Beta blockers are beta males who are stinky sweaters!!!!!!!

Adrenergic symptoms = A FOR ANXIETY

• These occur first, followed by neuroglycopenic symptoms

• MAY NOT OCCUR in ppl with impaired awareness of hypoglycemia

  • Trembling, palpitation, swearing, anxiety, hunger, nausea, tingling

Neuroglycopenic = THINK OF A DRUNK PERSON

• Difficulty concentrating, confusion, weakness, drowziness, slurred speech, headache, dizziness

• Treatment: "Rule of 15" → 15g sugar (e.g., juice, glucose tabs), wait 15 min, recheck

  • If after 3 attempts you’re still hypoglycemic, GO TO HOSPITAL !!! YOU FAILED YOURSELF DUMMY.

• Prevention: Eat regular meals, adjust meds if needed

1) LEVEL 1 HYPOGLYCEMIA

• Glucose level below normal (3-3.9)

• Autonomic symptoms present , no neuroglycopenic symptoms

2) LEVEL 2 HYPOGLYCEMIA

• Glucose level below normal (<3)

• Neuroglycopenic symptoms without significant impact on mental status (they ain’t going psycho)

• Autonomic symptoms may or may not be present

3) LEVEL 3 HYPOGLYCEMIA

• Glucose levels VERYYY BELOW normal

• Neuroglycopenic symptoms that are BAD (altered physical / mental status)

• Requires assistance to treat

COUNSELLING TIPS:

• Important esp for bozos on sulfonylureas, meglitinides, insulin

• Review possible causes w them (delayed meal, increased activity, drugs, alcohol)

REDUCING HYPOGLYCEMIA RISK DURING EXERCISE

1. Reduce bolus dose of insulin at time of exercise

2. Reduce or suspend basal insulin for exercise duration (if activity < 45 minutes)

3. Lower basal rate overnight after exercise by ~20%

4. Increase carbohydrate consumption prior to, during, and after exercise as necessary

**BASIC TIPS —> Just reduce both types of insulin and eat like a fatty mc fatty bc I guess you ain’t gonna be at a net calorie deficit when u exercise LOSERRRR

HYPOGLYCEMIA AND DRIVING

You gotta be 5 to drive —> (Levels <5 = DO NOT DRIVE)

11. When to Start Insulin & How to Adjust

We start insulin when other meds aren’t enough (A1C is above target AND patient is on 2-4 maximal doses of non insulin medications)

• Starting dose: Basal insulin (e.g., glargine) at 10 units/day or 0.1-0.2 units/kg (5-10 units at bedtime)

  • Most people will eventually require 25-50 units of basal insulin

• Adjusting: Increase by 1 unit each morning if blood glucose above 7, check A1C in 3 months

For complex cases (mealtime insulin), we follow a basal-bolus regimen based on carbohydrate intake and blood sugar levels.

DISCONTINUING MEDICATIONS WHEN STARTING INSULIN ?

• Don’t discontinue other diabetes medications UNLESS its

  • Rosiglitzone or Pioglitazone

    • in which case…. u should prob discontinue lol

BOLUS INSULIN (Nutritional Insulin)

• Start with 2 units w/ largest meal (or meal that has highest postprandial reading)

• Adjust weekly —> Eventually most ppl have 50% basal 50% bolus

• DISCONTINUE OR REDUCE DOSE of sulfonylureas, repaglinide (to decrease risk of hypoglycemia)

12. Type 1 vs. Type 2 Diabetes

1. How often should blood glucose levels be measured?

🔹 Depends on type of diabetes & medications:

GENERALLY:

• Check once daily for once a day injections

• Twice daily for twice a day injections etc

✅ Exception: If sick, fasting, or changing meds → check more frequently!

2. What is an appropriate 2nd line and 3rd line agent in a person with diabetes?

After metformin, the choice depends on patient factors:

• If heart disease or kidney disease? 🚨 → SGLT2 inhibitor (-flozin) or GLP-1 RA (-tide)

• If weight loss is needed? 🏋 → GLP-1 RA or SGLT2i

• If cost is an issue? 💰 → Sulfonylurea or TZD

• If avoiding hypoglycemia? ⚠ → DPP-4i, GLP-1 RA, SGLT2i

🔹 3rd line = add another agent from a different class if A1c is still high.

3. What patient factors should be considered when choosing diabetes meds?

• Heart/kidney disease? → SGLT2i/GLP-1 RA for protection

• Hypoglycemia risk? → Avoid sulfonylureas & insulin

• Weight loss goal? → Use SGLT2i/GLP-1 RA

• Cost issues? → Sulfonylureas/TZDs are cheaper

• Elderly/fall risk? → Avoid sulfonylureas & high insulin doses

4. When should insulin be initiated?

🛑 Start insulin when:

• A1c ≥ 10% OR fasting glucose > 16.7 mmol/L

• Symptoms of hyperglycemia (weight loss, excessive thirst/urination, fatigue)

• Oral meds aren’t enough anymore

5. How should insulin be dosed & adjusted?

🔹 Starting dose (basal insulin):

• 10 units/day OR 0.1–0.2 units/kg/day

• Adjust by 1–2 units every 3 days until fasting sugar reaches goal

🔹 If post-meal sugars are still high:

• Add bolus insulin before meals (start with 4 units & adjust)

6. Which insulin is best?

💡 Depends on patient needs!

🚨 Basal-first strategy is preferred in Type 2 diabetes.

7. What drugs increase the risk of diabetes?

⚠ Some meds can cause insulin resistance or increase blood sugar:

• Glucocorticoids (e.g., prednisone) → Most common!

• Antipsychotics (e.g., olanzapine, clozapine)

• Beta-blockers (mask hypoglycemia, may increase sugar)

• Thiazide diuretics (at high doses)

• Statins (slight risk but benefits outweigh it!)

8. What is the typical course of therapy in diabetes?

1⃣ Start with lifestyle changes (diet, exercise, weight loss)
2⃣ Metformin (unless contraindicated)
3⃣ Add second-line agent based on patient factors (SGLT2i, GLP-1 RA, sulfonylurea, etc.)
4⃣ If still high A1c, add a 3rd agent
5⃣ If still uncontrolled, start basal insulin
6⃣ If needed, add mealtime insulin

9. Hypoglycemia – Definition, Symptoms, Management, Prevention

• Definition: Blood sugar <4.0 mmol/L

• Symptoms:

  • Mild: Shaky, hungry, fast heartbeat

  • Moderate: Confused, weak, blurred vision

  • Severe: Seizures, unconsciousness

• Management: "Rule of 15"

  1. Eat 15g of fast sugar (glucose tabs, juice, candy)

  2. Wait 15 min, recheck sugar

  3. Repeat if needed

• Prevention: Eat regularly, adjust meds, avoid excess alcohol

10. What about alcohol and diabetes?

🚨 Alcohol can cause hypoglycemia, especially with insulin/sulfonylureas!

• Drink with food to prevent sugar crashes

• Limit to ≤2 drinks/day

• Monitor sugar carefully

11. Should DPP-4 inhibitors still be used?

✅ They’re still an option but…

• Weaker than SGLT2i & GLP-1 RA

• No heart/kidney benefits

• Main use: If a patient can’t tolerate SGLT2i or GLP-1 RA

12. Should sulfonylureas still be used?

✅ Yes, but selectively:

• Good for cost-conscious patients

• Works well but risk of hypoglycemia & weight gain

• Use gliclazide (better safety than glyburide/glimepiride)

Summary

• Blood sugar monitoring varies by diabetes type & meds

• 2nd/3rd line agents depend on patient factors

• Insulin is started when A1c ≥10% or symptoms appear

• Basal insulin first, adjust slowly

• Certain meds increase diabetes risk

• DPP-4i & sulfonylureas still have a role but aren’t first choice

• Hypoglycemia must be treated & prevented

• Alcohol can worsen diabetes control

What Happens If My Blood Sugars Stay High?

If diabetes isn’t properly managed, high blood sugar over time damages blood vessels, leading to two main types of complications:

1⃣ Microvascular (Small Vessel Disease) 🏥

• Eye damage (retinopathy, cataracts) 👁 → Can lead to blindness

• Kidney disease (nephropathy) 🩸 → Can lead to dialysis

• Nerve damage (neuropathy) ⚡ → Can cause numbness, pain, and increase risk of amputations

• Foot problems 🦶 → Poor healing + nerve damage = infections & ulcers

2⃣ Macrovascular (Large Vessel Disease) 💔

• Heart disease & high blood pressure ❤ → Increased risk of heart attacks

• Stroke 🧠 → Poor blood flow to the brain = major disability risk

Why does this matter?

✅ Proper management (meds + lifestyle) can delay or prevent these complications and help people live longer & healthier lives!

Does Lowering Blood Sugars Always Help? 🤔

🔹 It depends—lowering blood sugar is important, but too aggressive control can sometimes be harmful!

🔬 Key Trials to Know:

1⃣ ACCORD Trial 🏥

• Found that pushing A1c too low (<6.0%) too quickly actually increased the risk of death in some people (esp. those with heart disease).

• Lesson? Don’t chase perfect numbers—balance is key!

2⃣ Rosiglitazone Meta-Analysis 💊

• This diabetes drug (rosiglitazone) lowered A1c but increased the risk of heart attacks!

• Lesson? Lowering sugar alone is NOT enough—we need meds that also protect the heart!

3⃣ SAVOR-TIMI 53 (Saxagliptin Trial) 📊

• Showed that saxagliptin (DPP-4 inhibitor) lowered blood sugar, but increased the risk of heart failure.

• Lesson? We must consider long-term outcomes, not just glucose control.

🔹 Bottom Line: Managing diabetes isn’t just about sugar levels—it’s about preventing long-term harm!

Do We Need to Screen for Type 1 Diabetes?

❌ No screening needed!

• Why? No proven way to prevent or delay Type 1 diabetes even if we catch it early.

Who Should Be Screened for Type 2 Diabetes?

✅ Screen everyone ≥40 years old OR those at high risk!

• How? Use a Fasting Plasma Glucose (FPG) and/or A1c test every 3 years.

• If high risk? (33% chance of diabetes in 10 years) → Screen earlier & more often!

How Do We Diagnose Diabetes?

If someone doesn’t have symptoms, diabetes is diagnosed if any two of these are met:

🚨 If symptoms are present (thirst, urination, weight loss, etc.), ONE abnormal test is enough!

Symptoms of Diabetes

⚠ Not everyone has symptoms! But when they do, they might experience:

High Blood Sugar Symptoms (Hyperglycemia) 🚨

• Excessive thirst (polydipsia) 🥤

• Frequent urination (polyuria) 🚽

• Unexplained weight loss or gain ⚖

• Extreme fatigue 🛏

• Blurred vision 👀

• Frequent infections 🦠 (UTIs, yeast infections, etc.)

• Slow healing cuts & bruises 🩹

• Tingling/numbness in hands & feet 🦶

• Erectile dysfunction in men 🍆

💡 Remember: Some people don’t have symptoms at all, which is why screening is important!

📝 Main Takeaways:

✅ Untreated high sugars = microvascular & macrovascular complications (eye, kidney, nerve, heart, stroke)
✅ Lowering sugar too aggressively can be dangerous! (ACCORD, Rosiglitazone, SAVOR-TIMI)
✅ Screen for Type 2 diabetes every 3 years in people ≥40 or high risk
✅ Diagnose diabetes with 2 abnormal A1c or fasting glucose tests OR 1 test if symptoms present
✅ Symptoms: Excess thirst, urination, fatigue, infections, slow healing, numbness, vision issues

Clinical Features – How Do They Differ?

📌 Key Takeaway:

• Type 1 diabetes → Insulin-dependent from the start

• Type 2 diabetes → Lifestyle & meds first, insulin later if needed

• MODY → Genetic, may need different treatments

Diagnosing Diabetes 🩸

🔹 A person is diagnosed with diabetes if they meet ONE of these criteria:

Confirming the Diagnosis

🔹 If NO symptoms:

• Repeat the test on a different day to confirm.

• If using different tests (e.g., one A1C and one FPG), and both are above the cutoff → diagnosis confirmed.

🔹 If symptoms ARE present (thirst, urination, weight loss, etc.):

• Diagnosis is confirmed immediately—no second test needed!

🚨 For suspected Type 1 diabetes (especially in young, thin, or very symptomatic patients), treatment should start immediately—DO NOT delay for confirmatory tests!

A1C – The Gold Standard for Diabetes Control 🎯

🔹 What is A1C?

• Measures the % of hemoglobin (HbA1c) bound to glucose in red blood cells.

• Reflects average blood sugar over the past 3 months.

📌 A1C is a ‘surrogate marker’ for complications: Lower A1C → Lower risk of diabetes complications!

Pros & Cons of A1C

✅ Advantages:
✔ No fasting required (convenient)
✔ Only needs testing every 3-6 months
✔ Easier for long-term tracking

⚠ Disadvantages:
❌ Does NOT show daily fluctuations (someone could have extreme highs & lows, but A1C looks fine)
❌ Not accurate in certain conditions:

• Hemoglobinopathies (e.g., sickle cell disease)

• Severe kidney disease

• Pregnancy (not used to diagnose gestational diabetes)
  ❌ Ethnicity & age can affect results

🔹 Fasting Blood Glucose vs. A1C – Which is Better?

• Fasting glucose → Shows blood sugar at that exact moment.

• A1C → Shows long-term control, but doesn’t reflect daily ups & downs.

📌 Best approach? Use both fasting glucose & A1C to get the full picture!

What’s a Good A1C? 🎯

🔹 A1C in a person WITHOUT diabetes? 4.5-5.9%
🔹 Targets for people WITH diabetes:

🚨 A1C should NOT be the only factor—consider overall health & risk of low blood sugar!

🏆 Key Takeaways for Your Exam

✅ Types of diabetes:

• Type 1 → Autoimmune, insulin-dependent

• Type 2 → Insulin resistance + secretion problem, treated with meds/lifestyle first

• Gestational → Pregnancy-related, risk of future T2DM

• MODY → Genetic, may need different treatment

✅ How we diagnose diabetes:

• FPG ≥7.0, A1C ≥6.5%, 2hPG (OGTT) ≥11.1, or RPG ≥11.1

• If symptomatic → Only one test needed!

• If no symptoms → Confirm with a second test!

✅ A1C = Long-term diabetes control marker

• Pros: No fasting, every 3-6 months

• Cons: Doesn’t show daily swings, affected by some conditions

✅ A1C Targets:

• ≤6.5% (low-risk T2DM, prevents CKD/eye disease)

• ≤7.0% (most adults)

• 7.1-8.5% (elderly, frail, severe hypoglycemia risk)

When to Aim for A1C >7%?

A higher A1C target is considered to avoid hypoglycemia and over-treatment, particularly in these groups:

• Functionally dependent: 7.1-8.0%

• History of recurrent severe hypoglycemia (especially with unawareness): 7.1-8.5%

• Limited life expectancy: 7.1-8.5%

• Frail elderly and/or dementia: 7.1-8.5%

• End of life: A1C measurement not recommended; focus on avoiding symptomatic hyperglycemia and hypoglycemia

Reassessing Diabetes Medications

When adjusting treatment, consider:

• Is achieving A1C target still aligned with the patient's health goals?

• How far is their actual A1C from their individualized target?

• Are there medication side effects or increased risk of hypoglycemia?

• Is the patient on a sulfonylurea or insulin (which increases hypoglycemia risk)?

• Are any medications too burdensome or expensive for the patient?

Preprandial and Postprandial Glucose Targets for A1C ≤7.0%

Self-Monitoring of Blood Glucose (SMBG)

Key Takeaways:

• Routine SMBG is not required for most adults with type 2 diabetes on oral medications.

• SMBG is only useful if the results lead to a specific action (e.g., adjusting meds, diet, or insulin).

• If diabetes is managed through diet alone, routine SMBG is not required.

• For those using basal insulin, SMBG should be tailored, typically ≤14 tests/week for most patients.

Situations where SMBG may be needed:

• Multiple daily insulin injections

• Newly diagnosed or starting new medications/insulin

• History of or increased risk of hypoglycemia

• Acute illness

• Significant changes in routine or medications

• Unstable or poorly controlled blood glucose

• Pregnant or planning pregnancy

• Jobs where hypoglycemia is a safety risk

Frail Elderly & Long-Term Care (LTC)

• Blood glucose targets are different in frail elderly and LTC patients.

• Most people with type 2 diabetes not on insulin can self-test less often without harm.

• Testing may be more beneficial in specific cases (e.g., risk of hypoglycemia, routine/med changes, pregnancy).

Bottom Line

• Don't test if you're not going to act on the results.

• Individualize SMBG—some patients may benefit, but routine testing isn’t necessary for everyone.

• In frail elderly/LTC, A1C and blood glucose targets are more relaxed, and preventing hypoglycemia is the main priority.