Managing type 2 diabetes (T2D) often requires a multifaceted approach, combining lifestyle changes with medication when necessary. Typically, Metformin is prescribed when you’re diagnosed with T2D. When Metformin isn’t enough to lower your glucose to healthy levels, your doctor may suggest combination therapy.
With several medication classes available, each with its own history and unique benefits, it's important to understand the options to make informed treatment decisions. Because different drugs act in different ways to lower blood glucose levels, they may be used together to help meet your goals. For example, metformin and Sitagliptin (DPP-4 inhibitor) may be used together to help keep blood glucose levels at goal. That said, many combinations can be used.
Metformin: First-Line Treatment Option
- Drug class: Biguanides
- Examples: Metformin is the only medication in this class
- Retail Cost: $4-$15
- A1C Reduction: Reduces A1C levels by about 1% to 2% when used as monotherapy. When combined with other medications, it can provide additional A1C reduction.
Metformin has been a mainstay in T2D management since its discovery in the 1920s. Its use expanded in the 1950s, and it gained widespread popularity in the 1990s due to its efficacy, safety profile, and affordability.
Metformin remains the first-line medication for T2D and is often prescribed as the initial therapy and may be combined with other medications as the disease progresses.
Metformin works primarily by reducing the amount of glucose produced by the liver and increasing the sensitivity of muscle cells to insulin, thereby improving glucose uptake.
Common side effects of metformin include gastrointestinal symptoms like nausea and diarrhea. However, these usually improve over time and can often be managed with lifestyle modifications or changes in dosage.
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Sulfonylureas: Stimulating Insulin Production
- Drug class: Sulfonylureas
- Examples: Glipizide, glyburide, glimepiride
- Retail Cost: $6-$24
- A1C Reduction: Sulfonylureas lows A1C leves by approximately 1% to 2%. However, they may become less effective over time and can cause weight gain.
These drugs gained popularity for their ability to stimulate insulin secretion from the pancreas to lower blood sugar levels. Sulfonylureas were once the mainstay of T2D treatment and remain widely prescribed today, especially as second-line agents when metformin alone is insufficient. However, their popularity has waned in recent years with the emergence of newer drug classes offering additional benefits.
Common side effects of sulfonylureas include hypoglycemia (low blood sugar), weight gain, and gastrointestinal upset. They may also carry a risk of cardiovascular events, particularly in high doses or in individuals with pre-existing heart conditions.
Glipizide, glyburide, and glimepiride are on our Wholesale Price List
- $37 for 180 tablets or $70 for 360 tablets
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DPP-4 Inhibitors: Targeting Incretin Pathway
- Drug class: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
- Examples: JANUVIA & ZITUVIO (sitagliptin), KOMBOLYZE (saxagliptin), TRADJENTA (linagliptin)
- Retail Cost: $550-$760
- A1C Reduction: DPP-4 inhibitors typically lower A1C levels by about 0.5% to 1%, with some variability among individual medications. They are often used as second-line therapy to provide additional A1C reduction when combined with other medications.
DPP-4 inhibitors entered the T2D treatment landscape in the early 2000s. These drugs gained attention for their novel mechanism of action: they enhance body’s natural ability to lower glucose levels. These medications block the enzyme DPP-4, which increases the levels of incretin hormones in the body. These hormones stimulate insulin release and inhibit glucagon secretion, leading to lower blood sugar levels.
DPP-4 inhibitors quickly gained popularity as second-line options. They are typically well-tolerated and have a low risk of causing hypoglycemia (low blood sugar) when used alone or in combination with metformin. While not as widely prescribed as metformin or sulfonylureas, DPP-4 inhibitors remain a popular choice due to their favorable side effect profile.
Side effects of DPP-4 inhibitors may include upper respiratory tract infections, headache, and nasopharyngitis. While generally well-tolerated, there may be a low risk of pancreatitis or joint pain.
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SGLT-2 Inhibitors: Blocking Glucose Reabsorption
- Drug class: Sodium-Glucose Co-Transporter-2 (SGLT-2) Inhibitors
- Examples: BRENZAVVY (bexaglifloxin) INVOKANA (canagliflozin), FARXIGA (dapagliflozin), JARDIANCE (empagliflozin)
- Retail Cost: $520-$720
- A1C Reduction: SGLT-2 inhibitors can lower A1C levels by approximately 0.5% to 1%. In addition to glycemic control, they offer cardiovascular and renal benefits. However, individual responses may vary.
SGLT-2 inhibitors, such as BRENZAVVY, emerged in the 2010s as a new class of T2D medications. Unlike previous drug classes that primarily target insulin secretion or sensitivity, SGLT-2 inhibitors act on the kidneys to inhibit glucose reabsorption, leading to increased urinary glucose excretion.
SGLT-2 inhibitors have gained popularity in recent years, particularly for their cardiovascular and renal benefits beyond glycemic control. Clinical trials have demonstrated reductions in the risk of cardiovascular events and progression of kidney disease in individuals with T2D and established cardiovascular disease or chronic kidney disease.
The most common side effects of SGLT2 inhibitors include an increased risk of genital and urinary tract infections, such as yeast infections in women and urinary tract infections in both men and women. Patients may also experience increased urination and thirst. Additionally, a mild to moderate decrease in blood pressure, potentially causing dizziness or fainting, is another common side effect.
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GLP-1 Receptor Agonists: A Newer Approach
- Drug class: Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists
- Examples: : BYETTA (exenatide), VICTOZA (liraglutide), OZEMPIC & RYBELSUS (semaglutide), MOUNJARO (tirzepatide)
- Retail Cost: $900-$1,300
- A1C Reduction: GLP-1 agonists lower A1C levels by 1% to 1.5%. They also promote weight loss and have a lower risk of hypoglycemia compared to some other medications.
The history of GLP-1 agonists dates back to their introduction to the market in the early 2000s. Initially, their use was limited due to the inconvenience of daily dosing schedules and other practical considerations. However, the landscape changed dramatically with the arrival of Ozempic, which entered the market in 2017. Ozempic revolutionized the class of GLP-1 agonists with its improved dosing schedule, offering an once-weekly injection regimen compared to previous daily dosing requirements. This dosing convenience, coupled with its improved efficacy in lowering blood sugar levels and promoting weight loss, propelled Ozempic to the forefront of T2D management.
These drugs mimic the action of GLP-1, stimulating insulin secretion, inhibiting glucagon release, and slowing gastric emptying. Ozempic, approved in 2017, offers the convenience of once-weekly dosing.
Additionally, Rybelsus is the first and only oral medication (once daily) in this drug class. Approved in 2019, Rybelsus offers a convenient alternative to injections, addressing one of the primary concerns associated with GLP-1 agonist therapy.
Common side effects may include nausea, vomiting, diarrhea, and injection-site reactions. Rare side effects may include pancreatitis and thyroid tumors.
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BRENZAVVY for Type 2 Diabetes
The primary mechanism of Brenzavvy's action involves increasing the elimination of sugar through urine. It does so by preventing the reabsorption of sugars by the kidneys, leading to the excretion of excess sugars in urine. The result is a reduction in blood sugar levels and a lower A1C, which reflects the average glucose levels over the past three months.
Read MoreGeneric Sitagliptin
For those managing Type 2 Diabetes, DPP-4 inhibitors have become an important treatment option. Focusing on the body’s natural ability to regulate glucose levels, this drug class has significantly expanded the therapeutic options, offering a combination of efficacy, safety, and convenience.
However, the retail cost of these popular medications can be steep, often exceeding $600 per month, which puts them out of reach for many individuals.
Learn MoreDPP-4 Inhibitors vs. SGLT2 Inhibitors
DPP-4 Inhibitors enhance the body's natural ability to lower blood sugar levels. They work by helping the body produce more insulin and reduce the production of glucose in the liver.
SGLT2 Inhibitors assist the kidneys in removing excess glucose through urine. They do this by preventing glucose from being reabsorbed back into the blood from the kidneys.
Read MoreJardiance and other SGLT2 Inhibitors
There are several SGLT2 inhibitors available, and they each have subtle differences that determine when and how they should be used. These medications fall into four categories: bexagliflozin, canagliflozin, dapagliflozin, and empagliflozin. While there are ten branded versions, they come in various forms and can be combined in different ways, giving you more choices.
Read MoreOzempic vs Mounjaro
The main difference is the active ingredients they use. Ozempic uses semaglutide as the active ingredient which mimics the effects of GLP-1 while Mounjaro’s active ingredient, tirzepatide, mimics the effects of both GLP-1 and GPI. Since tirzepatide mimics two hormone groups, it’s called a dual GIP and GLP-1 receptor agonist or a ‘twincretin’ medication.
Read MoreRybelsus Tablet vs Ozempic Injection
Since they contain the same active ingredient, Rybelsus and Ozempic work the same way. In what ways are they different? The main differences are their dosage forms (convenience), some side effects, and cost, depending on your dose.
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