Dr. Ahmed The ADA 2023 statement regarding the pharmacological approach and Type 2 Diabetes Medications is summarized and presented in a simplified form here [Ref].
It is recommended for all individuals with Type 2 diabetes to follow a healthy lifestyle, focus 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, 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 adjusted to achieve the target A1C and blood glucose levels.
Summary of the ADA 2023 Diabetes Medications Recommendations:
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Metformin is considered a first-line medicine for most patients unless there are contraindications or the patient is not tolerating it because of side effects.
Metformin is highly effective in lowering A1C levels and is one of the cheapest medicines.
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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:
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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 exist. If Insulin is recommended, it is best to use a combination of insulin and a GLP-1 agonist for the following benefits:
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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.
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 |
Type 2 Diabetes Medications Classification Based on Their Efficacy:
Efficacy of Type 2 Diabetes Medications (in descending order) | Class | Examples |
| Intermediate | DPP-IV Inhibitors |
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| Intermediate to high | SGLT2 Inhibitors |
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| High | Metformin |
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| Thiazolidinediones |
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| 2nd Generation Sulfonylureas |
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| High to very highly effective | GLP-1 Receptor agonists |
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| Insulin |
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| Very high potency | GIP and GLP-1 Receptor agonists |
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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 |
| No effect | No |
| SGLT2 Inhibitors |
| Weight loss (Intermediate efficacy) | No |
| Biguanides |
| Neutral (may cause weight loss) | No |
| Thiazolidinediones |
| Weight gain | No |
| 2nd Generation Sulfonylureas |
| Weight gain | Yes |
| GLP-1 Receptor agonists |
| Weight Loss (Intermediate to very highly effective) | No |
| Insulin |
| Weight gain | Yes |
| GIP and GLP-1 Receptor agonists |
| Weight Loss (very highly effective) | No |
Type 2 Diabetes Medications: Cardiovascular and Renal Effects:
Class | Examples | Cardiovascular effects | Renal effects |
| DPP-IV Inhibitors |
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|
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| SGLT2 Inhibitors |
| 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 |
| 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 |
| Increases the 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 |
| 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, and Semaglutide are beneficial in reducing MACE. Exenatide and Lixisenatide are Neutral Neutral effect on heart failure. | Beneficial effects (Dulaglutide, Liraglutide, and Semaglutide) |
| Insulin |
| Neutral | Neutral effect Low insulin doses required |
| GIP and GLP-1 Receptor agonists |
| Under investigation | Under investigation |
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:
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| No comorbid | Metformin Metformin combination therapy | Add any of the following based on the glycemic goals Efficacy very high
Intermediate efficacy |
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