Diabetes is a serious condition that is brought on by decreased insulin secretion from the pancreas and diminished insulin sensitivity in the muscle cells. It is characterized by excessive urination, extreme thirst, high blood sugar, and increased appetite.1

There are a number of medications on the market to help manage this condition, but the following are the top 10 in terms of showing efficacy in lowering A1C and blood sugar levels.

1. Insulin (long- and rapid-acting)
Patients with type 1 diabetes (T1D) must be treated with insulin, as the beta cells in their pancreas no longer produce it. Insulin plays a vital role in glucose uptake and is required by the muscle and adipose tissue.2 However, insulin is not solely for patients with T1D; those with type 2 diabetes (T2D) may also be placed on insulin but generally only after failing to reach glycemic targets upon being placed on multiple oral agents for some time. Patients with diabetes typically receive multiple injections per day, including bolus insulin administered before meals and the long-acting basal insulin that lowers blood sugar levels over time. Insulin is classified as a high-risk drug because it can cause patients to experience hypoglycemia, but the benefits of this treatment surely outweigh the risks.2

The most common insulins I see prescribed in my daily practice are Basaglar (long-acting) and NovoLog (rapid-acting).

2. Metformin (biguanide class)
Metformin is considered the first-line oral agent for patients with diabetes and can be used to treat pre-diabetes. It works by decreasing glucose production in the liver, increasing insulin sensitivity, and lowering intestinal sugar absorption. Metformin has been shown to decrease A1 levels by 1% to 2%, fasting glucose levels by an average of 25%, and postprandial glucose levels by 44%.3 Depending on the severity of the condition, prescribers may try metformin combined with lifestyle modifications as monotherapy before adding more oral agents to their patients’ medication regimens. The drug itself is well tolerated, though in the beginning patients may experience gastrointestinal upset, such as abdominal cramping, diarrhea, and flatulence.

3. Glipizide (sulfonylurea class)
If the A1C level is not at target after 3 months of using metformin, a prescriber may then choose to add glipizide to a patient’s regimen. This medication works by stimulating insulin secretion from the beta cells in the pancreas, which then causes a decrease in postprandial blood glucose. Glipizide is used for the treatment of T2D; it is contraindicated in T1D because it cannot be combined with insulin, which, as previously noted, is a required treatment for all T1D. When combined with insulin, glipizide causes severe hypoglycemia, which should be avoided. The drug has been shown to reduce A1C levels by 1% to 2% and works best when taken 30 minutes before a meal.4 When on glipizide, a patient may experience nausea and weight gain. The agent is very effective, especially at increasing insulin secretion, but its efficacy decreases after long-term use, as the beta cell function may start to decline.

4. Glimepiride (sulfonylurea class)
Glimepiride works in the same manner as glipizide, but is not typically combined with metformin as there is an increased risk of hypoglycemia when they are used together. Glimepiride is a once-daily medication and should be taken with the first main meal of the day. The drug works best when combined with a proper diet and exercise. Of all the sulfonylureas, glimepiride is associated with the least amount of weight gain and is preferred for patients with cardiovascular disease, as it lacks any damaging effects on ischemic preconditioning.

5. Invokana (sodium glucose cotransporter 2 inhibitor class)
If a patient has a sulfa allergy the previous 2 options are not suit- able, but this one may be. Invokana works by inhibiting the sodium glucose cotransporter 2 (SGLT2), which causes a reduction in the reabsorption of filtered glucose. The drug also causes the patient to excrete excess glucose through their urine, lowering plasma glucose concentrations overall. This medication has been shown to lower A1C levels by 0.7% to 1% but is particularly favored by most patients because of the significant weight loss it can bring about.

There are a few downsides to Invokana, however, as it increases thirst and urination. Patients may also experience more frequent infections, such as urinary tract infections (UTIs), because of the amount of sugar being excreted in their urine; as we know, bacteria love sugar. This medication is also frequently paired with metformin and has its own combination drug on the market called Invokamet, which can be costly. Patients can find coupons for Invokana on the manufacturer’s website, which may make treatment more affordable if they qualify.

6. Jardiance (SGLT2 class)​​​​​​​
Jardiance works in the same way as Invokana but may be the preferred option in patients with renal impairment as it reduces the risk for new or worsening kidney disease by 39%.3 In clinical trials, Jardiance also demonstrated decreased hospitalization rates from heart failure in at least 40% of patients, which is something to keep in mind when selecting which SGLT2 is best for each patient.

7. Januvia (dipeptidyl peptidase 4 inhibitor)​​​​​​​
Januvia works by regulating blood glucose levels by increasing the release of insulin from the beta cells and decreasing the secretion of glucagon. Januvia ultimately enhances the body’s own incretins. This drug has been shown to reduce A1C levels by 0.5% to 0.8% and significantly decrease postprandial blood glucose levels.4 It also is weight-neutral, which is a plus. Patients on Januvia may experience edema, rash, and UTIs. Although the medication can be costly, coupons are widely available.

8. Pioglitazone (thiazolidinediones)​​​​​​​
Pioglitazone works by increasing peripheral insulin sensitivity. It also has been shown to decrease A1C levels by 0.5% to 1.4%.3 Although pioglitazone has very good efficacy in terms of getting patients to target, it is not the best option for some because it can cause or exacerbate heart failure. Patients may experience nausea and stomach upset when taking this medication.

9. Victoza (glucagon-like peptide 1 agonist)​​​​​​​
Victoza works by decreasing glucagon secretion, increasing glucose insulin secretion, and slowing gastric emptying. It is a daily injection given without regard to meals. This option has demonstrated significant weight loss in patients. Victoza has been shown to decrease A1C levels by 0.5% to 1.1% and reduce post- prandial blood glucose.3 Patients may experience nausea, which is the primary adverse effect that has been reported, but this is a well-tolerated injection.

10. Trulicity (glucagon-like peptide 1 agonist)

This option is relatively new and soon may be preferred over Victoza as it only needs to be injected once a week. It can be costly, however. The drug works in the same way as Victoza but requires fewer injections. Patients also will see weight loss with this medication, although it can cause pain and inflammation in the pancreas.

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REFERENCES
  1. Fourlanos S, Perry C, Stein MS, Stankovich J, Harrison LC, Colman PG. A clinical screening tool identifies autoimmune diabetes in adults. Diabetes Care. 2006;29(5):970-975. doi:10.2337/diacare.295970
  2. National diabetes statistics report. CDC. Updated February 14, 2020. Accessed June 23, 2020. https://www.cdc.gov/diabetes/data/statistics/statistics-report.html#:~:text=Total%3A%2034.2%20million%20people%20have,people%20(21.4%25%20 are%20undiagnosed
  3. Introduction: standards of medical care in diabetes––2019. Diabetes Care. 2019;42 (suppl 1):S1-S2. doi:10.2337/dc19-Sint01
  4. ​​​​​​​Handelsman Y, Bloomgarden ZT, Grunberger G, et al. American Association of Clinical Endocrinologists and American College of Endocrinology––clinical practice guidelines for developing a diabetes mellitus comprehensive care plan––2015. Endocr Pract. 2015;21(suppl 1):1-87. doi:10.4158/EP15672.GL