Anti-Diabetic

Januvia/Janumet (Sitagliptin)

Januvia in Dano Health view

Januvia/Janumet (Sitagliptin) in Dano Health view

sItagliptin previously identified as MK-0431 and marketed as the phosphate salt under the trade name Januvia is an oral Type 2 diabetes medication manufactured by Merck & Co. It was the first dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs that were approved by the FDA in 2006. This new oral hypoglycemic (anti-diabetic) drug is the top-selling brand in its class. JANUMET tablets consist of 2 prescription medicines: sitagliptin (JANUVIA®) and metformin.

Januvia in Dano Health view

Januvia in Dano Health view

History

On October 17, 2006: the U.S. Food and Drug Administration (FDA) approved  Sitagliptin.

On April 2, 2007: Merck & Co. marketed Sitagliptin in the US as Januvia and the FDA approved an oral combination of sitagliptin and metformin marketed in the US as Janumet.

In 2011:  the FDA approved an oral combination of sitagliptin and simvastatin marketed in the US as Juvisync. During this year, the FDA received almost 200 reports of acute and chronic pancreatitis that linked to Januvia and Janumet while some of them were fatal.

In 2013: the FDA announced it was studying the Januvia’s link to pancreatitis and possibly pancreatic cancer and they found that there was no cause for concern with safety risks in a new study linking Januvia and other DPP-4’s to pancreatitis. But they claimed that its review was ongoing.

In 2015, the FDA warned that Januvia and Janumet could cause severe joint pain.

Medical use

JANUVIA is a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise:

  • To improve glycaemic control in combination with metformin when diet and exercise plus metformin alone were not successful in glycaemic control.
  • To improve glycaemic control in combination with a Sulphonylurea (i.e., triple combination therapy) when diet and exercise plus a maximally tolerated dose of a Sulphonylurea alone were not successful in glycaemic control and when metformin is not appropriate because of contraindications or intolerance.
  • To improve glycaemic control in combination with a Sulphonylurea and metformin when diet and exercise plus dual therapy with these agents were not successful in glycaemic control.

Mechanism

JANUMET is an oral enzyme-inhibiting medicine that, along with diet and exercise, helps lower blood sugar in adults with type 2 diabetes. For lowering blood sugar, it:

  • Helps your pancreas make more insulin
  • Helps your body more effectively use the insulin that it makes
  • Helps decrease excess sugar that your liver makes

After a person eats, blood sugar rises and intestinal cells release incretin hormones that stimulate pancreatic cells called beta cells to release insulin. Insulin metabolizes sugar and sends signals to the liver to stop making excess sugar. DPP-4 breaks down incretin to keep blood sugar and insulin levels balanced but in patients with diabetes, too much sugar is already in the blood.

Januvia is a part of the class of diabetes medications called DPP-4 inhibitors. It blocks DPP-4, allowing incretin to stay in the blood longer and continue stimulating the pancreas into making more insulin to remove excess sugar.

Biosimilars

Now, there is no generic version of Janumet on the market, but depending on FDA approval, one may become available in November 2026. Also, there are comparable Gliptin and Biguanide combination drugs on the market with the same end results. They are Kombiglyze XR, Jentadueto, and Kazano. Dano Health as a clinical trial product distributor can provide Januvia for the companies who looking for it, too.

Difference between Metformin and Sitagliptin(JANUVIA®)

The mechanism of action of metformin and sitagliptin is completely different from each other. So their function, safety and side effect profiles are different, too. In the following table, some of the most noticeable differences are mentioned.

  Metformin Sitagliptin
Brand name/

Year of initial approval

Glucophage®, 1995 Januvia®, 2006
Drug class Antidiabetic agent
Biguanide Dipeptidyl peptidase-4 (DPP-4) inhibitor
Insulin secretagogue
Mechanism of action • Decreases hepatic glucose production
• Improves insulin sensitivity (increases peripheral glucose uptake and utilization)
• Reduce absorption of glucose in the gut
• Inhibits DPP-4 enzyme (the primary enzyme degrading the incretin hormones) resulting in prolonged active incretin levels, which regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta – cells and decreasing glucagon secretion from pancreatic alpha-cells.
Sitagliptin monotherapy requires intact ß-cells, it may be best used in people with early-stage diabetes.
Metformin and sitagliptin differently influence the metabolism of glycolipids after different diets.
Half-life 6.2 hours 12.4 hours
Oral bioavailability 50-60% 87%
Food Should be taken with meals Requires to be taken with food to work
Cost Very inexpensive Expensive

Market:

The patent on the drug will be expired in 2022. Januvia brought in about $6 billion in 2014 and with two million prescriptions written in 2011, it is expected that it eventually produces multi-billion dollar sales numbers.

Januvia and Janumet alongside first-line metformin are mainstays of Type 2 diabetes treatment.  It competes with AstraZeneca’s ($AZN) Onglyza and Eli Lilly’s ($LLY) Tradjenta within the DPP-4 class, but it has dominated those drugs for years.

In 2014, the FDA and European regulators tried to sweep aside some suspected links between Januvia and other incretin mimetics, and pancreatitis and pancreatic cancer. Januvia’s cardiovascular safety study TECOS claimed no additional heart risks for patients using the drug; it was a positive signal that could increase sales. According to Bernstein analyst Tim Anderson, this result could give the drug a 10% long-term boost.

Sitagliptin contributed about 15.2% of Merck’s total revenues for 1Q16, a ~0.4% increase over 1Q15 in terms of contribution. It is estimated that these drugs contribute ~15.9% of total revenues for 2Q16, and 15.7% of total revenues for 3Q16, reflecting a positive trend.

Total combined sales for these drugs were $1.4 billion in 1Q16, a 4% growth at constant exchange rates, offset by a 3% negative impact of foreign exchange that resulted in a 1.4% growth in revenues for these drugs in 1Q16 over 1Q15. In the below charts sales of these drugs are shown during 2015-2016.

Januvia in Dano Health view- Januvia & Janumet

Januvia in Dano Health view- Januvia & Janumet

Competitors for Januvia and Janumet are Onglyza, jointly manufactured by Bristol-Myers Squibb (BMY) and AstraZeneca (AZN), and Galvus by Novartis (NVS). Merck has also received marketing authorization for Marizev, a once-weekly DPP-4 inhibitor in Japan. Dano Health is also a Named-Patient drug wholesaler in Turkey.

Januvia is available as a brand name drug only; its generic version is not yet available. Januvia price is around $457for a supply of 30 tablets.

Januvia holds a 75% market share for US markets. Due to increased demand and the buying pattern of a few customers, its revenues increased by 9%. Outside the US markets, Januvia holds a 65% market share. Due to lower sales in emerging markets and Venezuela, reported growth in Europe and Japan was partially offset. Outside the US markets excluding Venezuela, its revenues increased by 5%.

It should be noted that Dano Health as a Turkish pharmaceutical distributor can provide Januvia.

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