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Type 2 Diabetes Medications: ADA 2023 Treatment Guidelines

Type 2 Diabetes Medications

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The ADA 2023 statement regarding pharmacological approach and Type 2 Diabetes Medications are summarized and presented in a simplified form here [Ref].

It is recommended for all individuals with Type 2 diabetes to follow a healthy lifestyle, focuse on body weight, and perform regular exercise.

In addition, physicians should encourage them to self-monitor blood glucose and the treatment should be patient-centered keeping in view all the aspects including the patient’s preference, affordability, and tolerance.

Type 2 diabetes medications should also be tailored to ensure cardioprotective, kidney protection, and vascular protection.

Weight management should be one of the priorities and weight loss approaches should be recommended to obese individuals.

Treatment goals should be defined and medications should be adjusted to achieve the target A1C and blood glucose levels.

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Summary of the ADA 2023 Diabetes Medications Recommendations: 

  • Metformin should be continued when initiated unless there are contraindications.
  • Some individuals may be directly started on combination therapy to achieve glycemic targets earlier without exposing them to hypoglycemia.

Metformin is considered a first-line medicine for most patients unless there are contraindications or the patients is not tolerating it because of side effects.

Metformin is highly effective in lowering A1C levels and is one of the cheapest medicines.

  • Insulin therapy may be considered on diagnosis in some patients including:
    • A1C of more than 10% (86 mmol/mol)
    • Blood glucose of 300 mg/dl or more (16.7 mmol/L)
    • Evidence of significant weight loss
    • Symptoms of hyperglycemia

Insulin therapy may be the best option for patients who are highly symptomatic and have lost significant weight.

Treatment should be patient-centered keeping in view the following factors:

  • Cardiac and renal effects of the drugs
  • Efficacy of the drugs
  • The risks of hypoglycemia
  • The weight-loss effects of type 2 diabetes medications
  • Cost and access to the drugs
  • The risks of side effects and the patient’s preferences.
SGLT-2 inhibitors and/ or a GLP-1 analog with established cardiovascular benefits are recommended as a part of a comprehensive cardiovascular risk reduction plan independent of A1C in patients with:

  • Established atherosclerotic cardiovascular disease
  • Indicators of high cardiovascular risk
  • Established kidney disease
  • Established heart failure

SGLT-2 inhibitors with established cardiovascular benefits include:

GLP-1 agonists that are highly effective and have demonstrated cardiovascular and renal benefits include:

Once-weekly Exenatide has demonstrated cardiovascular benefits but has no renal protective effects.

In adults with Type 2 Diabetes, a GLP-1 agonist is preferred to insulin when possible and no contraindications to the GLP-1 agonist exists.

If Insulin is recommended, it is best to use a combination of insulin and a GLP-1 agonist for the following benefits:

  • Better efficacy
  • Durability
  • Weight loss, and
  • Reduced risks of hypoglycemia

Insulin therapy should be adjusted but excessive uses of basal insulins should be avoided. Over-basalization of insulin is referred to when more than 0.5 units/kg of basal insulin is used or the total units of basal insulin are more than the prandial units.

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Type 2 Diabetes Medications List and their Approved Maximum Dosages:

Class

Drug

Dosage strength

The maximum approved daily dose

Biguanides Metformin 850 mg (IR)  2,550 mg 
1,000 mg (IR)  2,000 mg 
1,000 mg (ER)  2,000 mg 
2nd Generation Sulfonylureas Glimepiride  4 mg  8 mg 
Glipizide 10 mg (IR)  40 mg 
10 mg (XL/ER)  20 mg 
Glyburide  6 mg (micronized)  12 mg 
5 mg  20 mg 
Thiazolidinedione  Pioglitazone  45 mg  45 mg 
α-Glucosidase inhibitors  Acarbose  100 mg  300 mg 
Miglitol  100 mg  300 mg 
Meglitinides  Nateglinide  120 mg  360 mg 
Repaglinide  2 mg  16 mg 
DPP-4 inhibitors  Alogliptin  25 mg  25 mg 
Saxagliptin  5 mg  5 mg 
Linagliptin  5 mg  5 mg 
Sitagliptin  100 mg  100 mg 
SGLT2 inhibitors  Ertugliflozin  15 mg  15 mg 
Dapagliflozin  10 mg  10 mg 
Canagliflozin 300 mg  300 mg 
Empagliflozin  25 mg  25 mg 
GLP-1 RAs  Exenatide (extended-release)  2 mg powder for suspension or pen  2 mg
Exenatide  10 μg pen  20 μg 
Dulaglutide  4.5 mg mL pen  4.5 mg
Semaglutide  1 mg pen  2 mg
14 mg (tablet)  14 mg 
Liraglutide  1.8 mg pen  1.8 mg 
Lixisenatide  20 μg pen  20 μg 
GLP-1/GIP dual agonist  Tirzepatide  15 mg pen  15 mg
Bile acid sequestrant  Colesevelam  625 mg tabs  3.75 g 
3.75 g suspension  3.75 g 
Dopamine-2 agonist  Bromocriptine  0.8 mg  4.8 mg 
Amylin mimetic  Pramlintide  120 μg pen  120 ug/injection

 

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Type 2 Diabetes Medications Classification Based on their Efficacy:

Efficacy of Type 2 Diabetes Medications (in descending order)

Class

Examples

Intermediate DPP-IV Inhibitors
  • Sitagliptin
  • Vildagliptin
  • Linagliptin
  • Alogliptin
  • Saxagliptin
Intermediate to high SGLT2 Inhibitors
  • Dapagliflozin
  • Empagliflozin
  • Canagliflozin
  • Ertugliflozin
High Metformin
  • Metformin
Thiazolidinediones
  • Pioglitazone
2nd Generation Sulfonylureas
  • Glyburide
  • Gliclazide
  • Glimepiride
High to very highly effective GLP-1 Receptor agonists
  • Dulaglutide
  • Liraglutide
  • Semaglutide
  • Exenatide
Insulin
  • Insulin analogs
  • Human Insulin
Very high potency GIP and GLP-1 Receptor agonists
  • Tirzepatide
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Type 2 Diabetes Medications: effects on body weight and risks of Hypoglycemia:

Class

Examples

Effect on weight

Hypoglycemia

DPP-IV Inhibitors
  • Sitagliptin
  • Vildagliptin
  • Linagliptin
  • Alogliptin
  • Saxagliptin
No effect No
SGLT2 Inhibitors
  • Dapagliflozin
  • Empagliflozin
  • Canagliflozin
  • Ertugliflozin
Weight loss (Intermediate efficacy) No
Biguanides
  • Metformin
Neutral (may cause weight loss) No
Thiazolidinediones
  • Pioglitazone
Weight gain No
2nd Generation Sulfonylureas
  • Glyburide
  • Gliclazide
  • Glimepiride
Weight gain Yes
GLP-1 Receptor agonists
  • Dulaglutide
  • Liraglutide
  • Semaglutide
  • Exenatide
Weight Loss (Intermediate to very highly effective) No
Insulin
  • Insulin analogs
  • Human Insulin
Weight gain Yes
GIP and GLP-1 Receptor agonists
  • Tirzepatide
Weight Loss (very highly effective) No
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Type 2 Diabetes Medications: Cardiovascular and Renal Effects:

Class

Examples

Cardiovascular effects

Renal effects

DPP-IV Inhibitors
  • Sitagliptin
  • Vildagliptin
  • Linagliptin
  • Alogliptin
  • Saxagliptin
  • Neutral
  • (Potential risks with Saxagliptin)
  • Neutral
  • Renal dose adjustment is required except for Linagliptin
SGLT2 Inhibitors
  • Dapagliflozin
  • Empagliflozin
  • Canagliflozin
  • Ertugliflozin
All SGLT2 inhibitors are beneficial in heart failure.

Canagliflozin and Empagliflozin are beneficial in reducing MACE (major adverse cardiovascular endpoints)

All SGLT2 Inhibitors except for Ertugliflozin prevent the progression of DKD (diabetic Kidney disease)
Metformin
  • Metformin
Potentially beneficial in reducing MACE.

Neutral effects in Heart failure

Neutral effect in preventing progression to DKD.

Contraindicated if GFR less than 30 ml/minute

Thiazolidinediones
  • Pioglitazone
Increases risk of heart failure

Potentially beneficial in reducing MACE.

Neutral effects in preventing progression to DKD

Not recommended in CKD due to fluid retention

2nd Generation Sulfonylureas
  • Glyburide
  • Gliclazide
  • Glimepiride
Neutral Neutral effect.

Glyburide is avoided in CKD.

Gliclazide and Glimepiride may be given with caution (risks of hypoglycemia)

GLP-1 Receptor agonists
  • Dulaglutide
  • Liraglutide
  • Semaglutide
  • Exenatide
Dulaglutide, Liraglutide, and Semaglutide are beneficial in reducing MACE.

Exenatide and Lixisenatide are Neutral

Neutral effect on heart failure.

Beneficial effects (Dulaglutide, Liraglutide, and Semaglutdide)
Insulin
  • Insulin analogs
  • Human Insulin
Neutral Neutral effect

Low insulin doses required

GIP and GLP-1 Receptor agonists
  • Tirzepatide
Under investigation Under investigation

 

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Choosing the best Type 2 Diabetes Medications for your patients:

To choose the best glucose-lowering medicine for your patients, consider their baseline comorbid conditions.

Choose the drugs that have renal and cardiac protective effects. The algorithm is outlined here.

Healthy lifestyle (Low-calorie diet, exercise), monitoring glucose, Diabetes Self Management

Comorbid condition

First-line

Second line

Heart Failure (HFrEF or HFpEF) SGLT2 inhibitors with proven benefits
ASCVD (Atherosclerotic cardiovascular disease) or indicators of high risk of ASCVD such as obesity, hypertension, smoking, dyslipidemia, age more than 55 years GLP-1 RA with proven benefits (Liraglutide, Dulaglutde, Semaglutide) If A1C is above targets, add SGLT2 Inhibitors
SGLT2 Inhibitors with CVD benefits If A1C is above targets, add GLP-1 RA
CKD SGLT2 Inhibitors except for Ertugliflozin GLP-1 RA with proven CVD benefits if SGLT2 is not tolerated or contraindicated
Overweight Lifestyle advice (medical nutrition therapy

Medications for weight loss

Metabolic surgery

Diabetes drugs for weight loss:

Efficacy very high:

  • Semaglutide
  • Tirzepatide

Efficacy high

  • Dulaglutide
  •  Liraglutide

Intermediate efficacy

  • GLP-1 RA (not listed above)
  • SGLT2 Inhibitors

Neutral effects

  • DPP-IV
  • Metformin
No comorbid Metformin

Metformin combination therapy

Add any of the following based on the glycemic goals

Efficacy very high

  • High dose dulaglutide
  • Semaglutide
  • Tirzepatide
  • Insulin
  • Combination oral or Injectable GLP-1 with Insulin

Efficacy high

  • GLP-1 RA not listed above
  • Metformin
  • SGLT2 Inhibitors
  • Sulfonylureas
  • Thiazolidinediones

Intermediate efficacy

  • DPP-IV inhibitors

 

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What do you think?

Written by Ahmed Farhan

I am an Internist practicing medicine for the last fifteen years. Over the years, I have learned that medicine is not about prescribing pills. True medical practice is helping people.
I do prescribe pills as well but the best results I get are when I motivate people to overcome their problems with little changes in their lifestyles.
Since most of my patients are obese and have diabetes, hypertension, and high cholesterol levels, I am writing at dibesity.com when free.
Dibesity, I know the correct word is diabesity. Ignore this! Be with us.
Also, you can contact me directly at dibesity.com@gmail.com

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