Type 2 Diabetes Medications: ADA 2023 Treatment Guidelines

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.

You may also like to read:

- Classification of Diabetes: ADA 2023 Updates
- ADA Glycemic Targets: 2023 Recommendations

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:

Semaglutide (Ozempic, Rybelsus)
Liraglutide (Victoza), and
Dulaglutide (Trulicity)

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.

You may also like to read:

- The ADA Diabetic Diet Recommendations
- Diabetes Medicines that Cause Weight Gain

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
	Glipizide	10 mg (XL/ER)	20 mg
	Glyburide	6 mg (micronized)	12 mg
	Glyburide	5 mg	20 mg
Thiazolidinedione	Pioglitazone	45 mg	45 mg
α-Glucosidase inhibitors	Acarbose	100 mg	300 mg
α-Glucosidase inhibitors	Miglitol	100 mg	300 mg
Meglitinides	Nateglinide	120 mg	360 mg
Meglitinides	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
	Semaglutide	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
Bile acid sequestrant	Colesevelam	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

You may also like to read:

- Signs Metformin is Working for Diabetes and PCOS
- Ozempic (Semaglutide Injection) and Rybelsus (Oral Semaglutide)

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
	2^nd Generation Sulfonylureas	Glyburide Gliclazide Glimepiride
High to very highly effective	GLP-1 Receptor agonists	Dulaglutide Liraglutide Semaglutide Exenatide
High to very highly effective	Insulin	Insulin analogs Human Insulin
Very high potency	GIP and GLP-1 Receptor agonists	Tirzepatide

You may also like to read:

- Tirzepatide (Mounjaro): Uses, Dose, MOA, Side effects, Cost
- Semaglutide Vs Liraglutide Vs Dulaglutide for Weight Loss

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
2^nd 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

You may also like to read:

- SGLT2 Inhibitors for Weight Loss in Non-Diabetics
- Best GLP-1 for Weight loss: Semaglutide and Liraglutide

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
2^nd 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

You may also like to read:

- Empagliflozin in Heart Failure with a Preserved Ejection Fraction (HFpEF)
- Jardiance Vs Farxiga: The Better Vs The Best SGLT2 Inhibitor

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, Dulaglutide, 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