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Type 2 Diabetes Treatments: Newer Medications

While metformin remains first-line treatment for type 2 diabetes, there are now two classes of medications to improve diabetes outcomes.

Treating Type 2 Diabetes—Is It Time to Consider Combination Therapy?

While most of you are likely to be taking metformin, which is considered first-line therapy for anyone with type 2 diabetes, gestational diabetes, and even prediabetes, it may not be enough as time goes on. Metformin works to improve insulin sensitivity and lessen glucose release and absorption, key activities involved in controlling diabetes.

However, every individual responds differently to the effects of metformin. Only one in four people will respond fully, while half find metformin helpful, and the remaining group finds little benefit in taking it. You’ll only know where you fit in to this medication response once you’ve begun taking this medication and checking in with your health care provider.

GLP-1RAs and SGLP-1 inhibitors are 2 types of drugs that can improve quality of life for people with type 2 diabetes.

Should You Consider Combination Therapy? Here's What You Need to Know

The overriding reason for anyone with type 2 diabetes to add a medication in addition to metformin is to help you better control your blood glucose. This in turn will help reduce your risk of developing common diabetes-related complications. 

If you have type 2 diabetes and are at increased risk for or diagnosed with heart disease, chronic kidney disease, and/or liver failure, it’s important to become familiar with all of your treatment options, so you are ready to discuss a more effective diabetes management plan with your doctor.

Type 2 Diabetes (T2D) is a metabolic disorder and an inflammatory state that can put you at higher-than-average risk of developing heart disease, chronic kidney disease (CKD) and a host of other common complications. The better and more consistently you are able to control your blood glucose levels, the lower your chances that these health problems will occur.

That’s why it’s still so important to make adjustments to your diet and step-up your physical activity. However, as essential as eating right and getting enough exercise to boost your heart and challenge your muscles, it is equally necessary to follow the best possible medical treatment to assure tight glycemic control and to address any worrisome risk factors.

When you’ve done all you can to establish good lifestyle patterns, yet the changes to your diet and exercise aren’t enough to get you into good blood sugar control, than you’ll want to add one of the new medications that will help prevent or at least minimize complications that can arise as your live with diabetes.1

“The goal of any drug therapy used to treat diabetes is to get your blood sugar levels as close to normal as possible and at the same time, to prevent or delay more complications in the future,” says David Nathan, MD, director of the Diabetes Center at Massachusetts General Hospital, and professor of medicine at Harvard Medical School in Boston.

The Advantages of Newer Diabetes Medications

If you have tight glycemic control and no complications, then your doctor will likely recommend sticking to the treatment plan you are currently following because it is working for you.

However, if you have T2D and are showing signs of heart disease or beginning to have issues with other organs, it is a very good idea to consider adding one or more of the newer medications, so-called second-line treatments, such as one of the glucagon-like peptide-1 receptor agonists (GLP-1RA) or sodium-glucose co-transporter-2 inhibitors (SGLT-2i).2,3

These two classes of drugs not only help control blood sugar but, in some cases, can help protect your heart, kidneys, and liver as well as foster greater weight loss,4 according to data from the American Diabetes Association. In fact, metformin is considered weight neutral, meaning it helps with glucose management but doesn’t promote weight loss in most people who take it.

GLP-1RAs: Benefits and Side Effects

Other key factors that may influence your decision to consider or reject this drug class include delivery formulations (ie, injection vs oral), and dosing requirements

GLP-1 medications impact blood glucose levels by exerting the following actions:

  • Increasing insulin production
  • Decreasing glucagon release
  • Slowing the rate at which food leaves the stomach
  • Feeling less hungry (having a sense of fullness) so that you feel satisfied with less food

Given the mechanisms by which these medications work, the end result is that most people will experience better blood sugar control as well as some weight loss, which is of course a welcome benefit from anyone with overweight.

There are several different GLP-1RAs available in this drug class:

  • Albiglutide (Tanzeum)
  • Dulaglutide (Trulicity)
  • Exenatide (Byetta)
  • Extended-release exenatide (Bydureon)
  • Liraglutide (Victoza)
  • Lixisenatide (Adlyxin)
  • Semaglutide (Ozempic)

In considering this group of medications, you should know that when taking one of these drugs, some people have reported experiencing gastrointestinal side effects, such as vomiting and diarrhea. These symptoms will likely go away after you've had time to adjust to the medication but you'll have to weight the pros against these cons when discussing all the options with your healthcare provider.

Until recently, GLP-1 was only available as an injectable medication but an oral formulation (available as a pill) now has FDA approval.x Depending upon your personal needs, the dosing schedule may be set at once a day, twice-daily, or one pill weekly, and depends upon which form of adminstration—oral or injection—you choose.

If adding another medication to your current treatment plan presents a problem for you, be sure to bring this concern up with your doctor so the type and frequency of your medication can be addressed to assure you have a disease management plan that will work for you.

SGLT-2i: Advantages and Disadvantages

There are four SGLT-2 inhibitors approved for use in individuals with type 2 diabetes in the United States: 

  • Canagliflozin (Invokana)
  • Dapagliflozin (Farxiga)
  • Empagliflozin (Jardiance)
  • Ertugliflozin (Steglatro)

This group of medications works by acting on the kidneys, so there is an increased eliminat\ion of blood sugar into the urine.

At the same time, this group of medications also helps to reduce blood pressure and promote weight loss. SGLT-2i are sometimes recommended for those with type 2 diabetes who not only have poorly controlled blood sugar from day to day but also have high A1C levels.

If you have or are at risk of developing chronic kidney disease, then an SGLT-2i may be recommended to slow the progression of this condition down; an SGLT-2i is a good choice so long as your glomerular filtration rate (a lab value that measure your kidney activity) is adequate.

One of the greatest benefit gained in taking these antidiabetes medications is in reducing your risk of hospitalization due to heart failure (31%) and lessening the progression of kidney disease (45%).4

While their effect on heart disease events is good, these types of drugs work best to reduce in major adverse cardiac events in patients with established heart disease not in individuals with no sign of cardiovascular disease. However, when it comes to hospitalization due to heart failure, the data are very strong for all patients with diabetes whether you have heart disease or a history of heart failure or not.

Similarly, a reduction in the development of renal disease is also strong in patients both with and without heart disease. However, in individuals taking an SGLT2i who have poorer renal function, there is a greater risk of hospitalization for heart failure.4

Possible Adverse Reactions When Taking SGLT2i

Potential side effects of SGLT-2i include genital yeast infections, urinary tract infections, constipation and flu-like symptoms. When combined with insulin or medications that increase insulin production, SGLT-2i can cause hypoglycemia. And while they have been shown in some cases to prevent progression to end stage kidney disease, they are not suitable for anyone with advanced CKD.5

“These are exciting new medications, and if you are an adult with poorly controlled type 2 diabetes despite diet and exercise modifications and the use of metformin, and you have established cardiovascular (heart) disease (CVD) or chronic kidney disease (CDK), one of the SGLT2 inhibitors may be right for you,” says John Kennedy, MD, chief medical officer of the American Medical Group Association. “Yet, they are not for everyone, and you can’t assume that you should be on one of these drugs just because you have T2D and CVD or CKD.”

Dr. Kennedy advises patients to review your current medical history and mediation list with your doctor to determine the safest and most effective treatment to meet your circumstances best. He also recommends that you check with your health insurer and pharmacist to understand what, if any, out-of-pocket costs might be expected of you, before you start taking any new diabetes medication.

Ask Questions, Seek Answers for More Personalized Care  

First and foremost, you should know what diabetes-related complications you may be facing as these risks will determine which medications are best for you.

In addition, when doctors consider which medications to prescribe to you—from among the standard and newer types of drugs—they should also consider your personal preferences, such as the timing of the medications in coordination with drugs you are already taking and the formulation of the drug (eg, do you prefer an occasional injection or a twice a day pill you have to swallow?).

They will also consider any drug intolerances, your overall health status, and any risk factors for developing diabetes-related complications.  

Most importantly, doctors need to be sure that the benefits of taking a particular medication outweigh any harm to the patient from possible risk of side effects, and lastly, they should consider the affordability of any medication they are going to add to your treatment plan.

If the cost is too high or you cannot afford the co-pay, there is no reason to write you a prescription for a drug you won’t be taking. Instead, the doctor must be sure that you are willing and able to take the medications as recommended.

Although doctors are advised to consider the practice guidelines of care developed by professional organizations, they must also consider how these treatment recommendations may affect you, and then tailor the general treatment to adjust for your specific needs.5

“When developing an appropriate diabetes treatment plan, physicians generally take their lead from their patients,” Dr. Nathan says; however, you can help by being well informed.

Tips for Communicating with Your Healthcare Team

If you are just taking metformin and want to consider expanding your treatment to include one of the drugs that will protect you from complications of diabetes, both Dr. Kennedy and Dr. Nathan encourage you to ask your doctor some questions to gain a better understanding of what would help you most. For example, you might say:

  • Could I benefit from taking either a GLP-1RA or SGLT-2i and, if so, what would the befits be? What risks might I face?
  • What risks should I be most concerned about avoiding given that I have type 2 diabetes?
  • Is there is any added benefit to my current treatment plan such as a better glucose lowering effect and/or increased protection from heart disease or chronic kidney disease?
  • If you are taking insulin, ask: does taking one of these new medications in combination with insulin or other glucose-lowering medications affect my dosage of these or any other medications?
  • Am I at greater risk for hypoglycemia if I am taking a sulfonylurea or metformin, and then add one of the newer medications?

Dr. Nathan suggests approaching the possibility of adding one these newer drugs cautiously because the benefits have not been shown for everyone and these medications are not necessarily recommended unless you already have been diagnosed with heart disease (or CVD or CKD and, even then, only in certain circumstances.

In addition to increasing the risk of experiencing dangerously low blood sugar, hypoglycemia can negatively alter your mood, energy levels, and memory, as well as raise concerns that you may develop kidney disease and heart conditions such as cardiac arrhythmia and vascular disease leading to stroke.

In combination with other medications (not related to diabetes), GLP-1RAs and SGLT-2is might increase the risk of hypoglycemia, so your doctor may need to check your blood sugar to adjust your dosages. So, if you doctor advises you to return for a follow up visit, do it! This is very important to assure that your care remains effective for you.

Can These Newer Medications Replace Metformin?

For most patients, metformin is considered first-line (standard) therapy for most everyone who is diagnosed with type 2 diabetes that is hard to controlled after you have done your best to adjust your diet and physical activity as advised by your doctor, registered dietitian, and/or certified diabetes educator.

Dr. Kennedy says: if your diabetes remains hard are to manage even after you begin taking metformin, or you cannot tolerate it or do not want to take it, some studies have shown that both GLP-1RAs and SGLT2i medications are both safe and effective glucose lowering treatments when compared to a placebo.

As for insulin—this remains an important treatment option for some patients with type 2 diabetes, particularly when you may be facing an acute (short-lived or passing) illness or for severe or problematic, longstanding diabetes. If a GLP-1RA or SGLT2i is initiated while you are taking insulin, you will need to monitor your blood sugar even more closely, and report any changes in your blood sugar readers to your doctor.

Can I Afford These Newer Medications? 

The cost of brand name medications can be very expensive if you have an insurance plan with high deductibles, including some Medicare plans, and if you do not have health insurance coverage. Even with insurance, the cost depends on the tier for your co-pay, and it will be several years before these medications are available in generic form at which time their prices are likely to decrease considerably.

If you have poorly controlled type 2 diabetes, and you can’t afford these new medications right now, your best option for treatment, according to the American Diabetes Association, is to consider taking sulfonylurea or thiazolidinedione medications, so long as there are no signs of heart disease or chronic kidney disease.6

To be sure that you able to participate fully as a partner in your diabetes treatment planning, tell your doctor and pharmacist about any concerns you have about your ability to pay for any new medications before anything is added to your treatment plan and prescribed for you.

Recommendations for the use of these newer diabetes medications will continue to evolve and may change as more studies are conducted. Therefore, it is important that you discuss any and all medical options with your doctor every so often in order to make sure that any adjustments that are needed related to your treatment goals are updated as necessary.   

Just to be certain that you are doing all you can be to reduce your risks of chronic diseases and getting the best possible individualized care, be sure that your primary care physician and all of your specialists are familiar with your full treatment plan.

That way, when you are faced with having to discuss any changes or additions to your diabetes treatment plan, especially when alternative medications are necessary or preferred, they will be prepared to communicate with each other to determine a comprehensive and holistic treatment approach that meets your needs fully.

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