There are a number of options available for oral medications, so let's take a look. These medications can help to lower blood sugar levels using a variety of mechanisms. They can also be used together in combination to improve outcomes as well as to reduce the risk of adverse effects. Let's start with biguanides:

Hyperglycemic control for patients who have type 2 diabetes when diet and exercise are not enough to attain glycemic control.

Mechanism of Action

Metformin decreases hepatic glucose production

It decreases the intestinal absorption of glucose

It improves insulin sensitivity, thus increasing glucose uptake and utilization

Metformin is a biguanide and has been the drug of choice for starting treatment in patients who have type 2 diabetes. The 2020 Standards of Medical Care in Diabetes continues to recognize metformin as the preferred initial treatment. There are many reasons why it is recommended as the first medication for newly diagnosed type 2 diabetes patients, including:

Considerable clinical experience with its use

Effectiveness

Relatively inexpensive (even free at certain pharmacies)

Low risk of hypoglycemia when used as monotherapy

Not associated with weight gain, and even offers possibility of weight loss or at least weight stabilization

Adverse effects, such as diarrhea, are typically mild and diminish after several weeks of therapy

Includes a possible protective effect against cardiovascular events in certain patient populations

The 2020 Standards of Care also recommend early combination therapy to extend the time to treatment failure. If glycemic control is not attained after three months of treatment with metformin and lifestyle interventions, another drug that employs a different mechanism to lower blood sugar levels may be added to the regimen. Should metformin as monotherapy show disappointing results, alternatives or adjuncts may be considered. Adjuncts may include sulfonylureas, thiazolidinedione, DPP-4 inhibitor, SGLT-2 inhibitor, GLP-1 receptor agonist, or basal insulin.

There is little head-to-head research comparing the efficacy and long-term safety of the second-line and third-line line diabetes medications, and there is little research about the advantages/disadvantages of any specific combination of oral hypoglycemics. Deciding which drug or drugs depends on several factors, and may include adverse effect profile, risks and benefits, comorbidities, and cost.

Beyond Metformin

Beyond metformin there are no set first-line drugs to use. From this point on it is all second- and third-line drugs, although there are no firm guidelines as to which ones should be used, or in what order. Most patients who have type 2 diabetes will need to use metformin and a second or third drug. Many patients who have type 2 diabetes will eventually need to use insulin.

Metformin is considered the first choice med for treating type 2 diabetes.

Basal insulin, GLP-1 receptor agonists, sulfonylureas, DDP-4 inhibitors, SGLT2 inhibitors, or thiazolidinediones are considered second-line drugs.

The α-glucosidase inhibitors, colesevelam, bromocriptine and pramlintide can be considered third-line drugs.

As we previously discussed, there is strong evidence that early administration of insulin can preserve pancreatic β-cell function and positively influence the course of type 2 diabetes. While many effective diabetes drugs have been on the market for years, new drugs may provide benefits that aren’t available with most commonly used drugs. Keep in mind, we may not yet know about all of the side effects and interactions of new drugs. Also, newer drugs may cost more than older drugs, and as a result may not yet be covered by most insurance plans. So, insurance plans may prefer certain drugs over others, or they may first require a trial of older, less expensive medications.