FDA Approves Trijardy XR (empagliflozin/linagliptin/metformin) for Type 2 Diabetes in Adults

In continuation of my update on empagliflozin/linagliptin/metformin 

    

The U.S. Food and Drug Administration (FDA) has approved Trijardy XR (empagliflozin/linagliptin/metformin hydrochloride extended release tablets) to lower blood sugar in adults with type 2 diabetes, along with diet and exercise. Trijardy XR provides three type 2 diabetes medicines in one pill, including Jardiance® (empagliflozin), Tradjenta® (linagliptin) and metformin hydrochloride extended release. Trijardy XR is marketed by Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY).

"Many adults living with type 2 diabetes who are already on a treatment plan including multiple medications still struggle to keep their blood sugar under control, and may require additional agents to reach their A1C targets," said Ralph DeFronzo, M.D., professor and diabetes division chief, UT Health San Antonio. "Adding new medicines to an individual's plan can be challenging for some, which is why new treatment options that can help improve blood sugar without the burden of an increased pill count are important. In addition, type 2 diabetes is a complex disease that often requires the use of multiple antidiabetic medications to improve glycemic control. Having three different diabetes medications in a single tablet is an important advance in diabetes treatment."

In the U.S., both Jardiance and Tradjenta are once-daily tablets used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. Jardiance is also approved to reduce the risk of cardiovascular death in adults with type 2 diabetes who have known cardiovascular disease. Jardiance is not for people with type 1 diabetes or for people with diabetic ketoacidosis (increased ketones in the blood or urine). Tradjenta is not for people with type 1 diabetes or for the treatment of diabetic ketoacidosis. Tradjenta has not been studied in people with a history of pancreatitis and it is unknown if using Tradjenta increases the risk of developing pancreatitis in these people. 

"We are proud to offer Trijardy XR as a new once-daily option combining three well-established medicines, including an extended-release version of metformin, the most commonly prescribed initial treatment for type 2 diabetes, Jardiance, the most prescribed SGLT2 inhibitor, and Tradjenta, the only single-dose DPP-4 inhibitor," said Mohamed Eid, M.D., M.P.H., M.H.A., vice president, Clinical Development & Medical Affairs, Cardio-Metabolism & Respiratory Medicine, Boehringer Ingelheim Pharmaceuticals, Inc. "We believe Trijardy XR has the potential to help adults with type 2 diabetes conveniently manage their treatment, especially those who are taking other medications and working on the necessary lifestyle changes."

Trijardy XR is not recommended for people with type 1 diabetes or diabetic ketoacidosis (increased ketones in the blood or urine). Trijardy XR has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using Trijardy XR. The labeling for Trijardy XR contains a warning for lactic acidosis, a rare but serious complication that can occur due to metformin accumulation, and is common to all products containing metformin.

The FDA approval of Trijardy XR is based on two randomized open-label trials that assessed the bioequivalence of empagliflozin, linagliptin and metformin hydrochloride extended release fixed-dose combination tablets and their individual components in healthy adults. The safety profile of Trijardy XR was found to be consistent with its individual components.

"The approval of Trijardy XR reflects our commitment to the diabetes community and to innovation that addresses evolving needs," said Jeff Emmick, M.D. Ph.D., vice president, Product Development, Lilly. "We developed Trijardy XR because many people with type 2 diabetes need help managing this complex condition without adding more pills to their treatment plan. We look forward to making this new option available soon."

Trijardy XR is not for people who have severe kidney problems, end stage renal disease, or are on dialysis, have a serious condition called metabolic acidosis or diabetic ketoacidosis (increased ketones in the blood or urine), or are allergic to Jardiance, Tradjenta, metformin, or any of the ingredients in Trijardy XR. There have been postmarketing reports of acute pancreatitis, including fatal pancreatitis, in patients taking linagliptin, a component of Trijardy XR. Take careful notice of potential signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue Trijardy XR and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using Trijardy XR.

Trijardy XR will be available in four different dosages, including: 5 mg empagliflozin/2.5 mg linagliptin/1000 mg metformin HCl extended-release; 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin HCl extended-release; 12.5 mg empagliflozin/2.5 mg linagliptin/1000 mg metformin HCl extended-release; and 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin HCl extended-release.

What is Trijardy XR?

Trijardy XR is a prescription medicine that contains 3 diabetes medicines, empagliflozin (JARDIANCE), linagliptin (TRADJENTA), and metformin hydrochloride. Trijardy XR can be used along with diet and exercise to lower blood sugar in adults with type 2 diabetes, and in adults with type 2 diabetes who have known cardiovascular disease when empagliflozin (JARDIANCE), one of the medicines in Trijardy XR, is needed to reduce the risk of cardiovascular death.

Trijardy XR is not for people with type 1 diabetes, or for people with diabetic ketoacidosis (increased ketones in the blood or urine).

If you have had pancreatitis (inflammation of the pancreas) in the past, it is not known if you have a higher chance of getting pancreatitis while you take Trijardy XR.

https://www.drugs.com/history/trijardy-xr.html

FDA Approves Qternmet XR (dapagliflozin, saxagliptin and metformin hydrochloride) for Type 2 Diabetes

In continuation of my update on dapagliflozin, and metformin hydrochloride

 

Dapagliflozin            Saxagliptin                                   and  (Metformin)

The US Food and Drug Administration (FDA) has approved Qternmet XR(dapagliflozin, saxagliptin and metformin hydrochloride) extended release tablets as an oral adjunct treatment to diet and exercise to improve glycaemic control in adults with type-2 diabetes (T2D).

The approval is based on two Phase III trials, which evaluated combinations of dapagliflozin and saxagliptin on a background of metformin over 24 weeks, in patients with inadequately-controlled T2D.

In one trial, treatment with 5mg dapagliflozin/5mg saxagliptin in addition to metformin demonstrated statistically-significant decreases in HbA1c (average blood glucose levels), and an increase in the number of patients achieving the recommended HbA1c treatment goal of <7%. In the second trial, treatment with 10mg dapagliflozin/5mg saxagliptin in addition to metformin extended release demonstrated statistically-significant decreases in HbA1c, and an increase in the number of patients achieving an HbA1c <7%.

The safety results of the individual medicines in these trials were consistent with their known profile.

About Qternmet XR

Qternmet XR is a once-daily, oral medicine compromised of the selective sodium‑glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin, the dipeptidyl peptidase‑4 (DPP‑4) inhibitor saxagliptin and metformin hydrochloride extended release. Qternmet XR is approved in the US as an adjunct to diet and exercise to improve glycaemic control in adults with type-2 diabetes.

https://en.wikipedia.org/wiki/Dapagliflozin

https://en.wikipedia.org/wiki/Saxagliptin

https://www.drugbank.ca/drugs/DB06335

https://www.drugbank.ca/drugs/DB00331

https://en.wikipedia.org/wiki/Metformin

FDA Approves Qternmet XR (dapagliflozin, saxagliptin and metformin hydrochloride) for Type 2 Diabetes

FDA Expands Indication For Type 2 Diabetes Treatment Synjardy (Empagliflozin/Metformin Hydrochloride) To Include Treatment-Naïve Adults

In continuation of my update on empagliflozin and metformin

The U.S. Food and Drug Administration has approved an expanded indication for Synjardy (empagliflozin and metformin hydrochloride) tablets to include treatment-naïve adults with type 2 diabetes (T2D). Synjardy, from Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY), is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D when treatment with both empagliflozin and metformin is appropriate.

empagliflozin Metformin

Synjardy is a combination of empagliflozin (Jardiance) and metformin — two medicines with complementary mechanisms of action — to help control blood glucose in adults with T2D. Empagliflozin, a sodium glucose co-transporter-2 inhibitor, removes excess glucose through the urine by blocking glucose re-absorption in the kidney. Metformin, a commonly prescribed initial treatment for T2D, lowers glucose production by the liver and its absorption in the intestine.

"Type 2 diabetes is a complex condition, which often requires that people take more than one treatment to manage their blood sugar," said Paul Fonteyne, president and CEO, Boehringer Ingelheim Pharmaceuticals, Inc. "The expanded indication for Synjardy further validates the potential of this combination therapy to help adults with type 2 diabetes who are not at goal, including those already being treated and, now, those at the beginning of their treatment journey."

The Synjardy label was updated to include results from a phase III, double-blind, randomized, active-controlled study that evaluated the efficacy and safety of empagliflozin in combination with metformin as initial therapy compared with the individual components. In the study, at 24 weeks, the combination of empagliflozin 10 mg or 25 mg with metformin 1000 mg or 2000 mg resulted in significant reductions in A1C (a measure of average blood glucose over the past two to three months) compared with the corresponding dose of either component alone.

Synjardy can cause serious side effects, including Lactic Acidosis (a buildup of lactic acid in the blood). Metformin, one of the medicines in Synjardy, can cause lactic acidosis, a rare, but serious condition that can cause death. Lactic acidosis is a medical emergency and must be treated in a hospital. Synjardy is not for the treatment of type 1 diabetes or diabetic ketoacidosis.

FDA Expands Indication of Invokamet (canagliflozin/metformin HCl) to Include First-Line Treatment of Type 2 Diabetes

In continuation of my updates on INVOKANA® (canagliflozin) and metformin hydrochloride,

Janssen Pharmaceuticals, Inc. (Janssen), announced the U.S. Food and Drug Administration (FDA) has approved Invokamet, a fixed-dose combination therapy of INVOKANA® (canagliflozin) and metformin hydrochloride, for first-line treatment of adults with type 2 diabetes. With this new approval, Invokamet may now be prescribed in adults with type 2 diabetes who are not already being treated with canagliflozin or metformin and may benefit from dual therapy.

 metformin    canagliflozin

Invokamet, the first combination of a sodium glucose co–transporter 2 (SGLT2) inhibitor and metformin available in the United States, was previously approved by the FDA in August 2014 as an adjunct to diet and exercise to improve blood glucose control in adults with type 2 diabetes not adequately controlled by either canagliflozin or metformin, or who are already being treated with both medications separately.

“Physicians increasingly try to achieve greater initial blood sugar control by using dual therapy at the outset, versus single-agent therapy alone, especially for patients with higher A1C levels,” said John Anderson, M.D.*, Frist Clinic, Nashville, Tenn. “Invokamet combines two effective, complementary medicines—canagliflozin and metformin—into one convenient pill, to lower A1C significantly more than metformin alone.”

A1C is a measure of average blood glucose over the past two to three months; the American Diabetes Association recommends most adults with type 2 diabetes maintain A1C levels of 7 percent or less.[2]

The new Invokamet indication aligns with recent type 2 diabetes treatment guidelines, which recommend dual therapy for patients with higher A1C levels. Specifically, guidelines recommend dual therapy for patients who have an initial A1C level of 7.5 percent or higher;[3] and for those who have an initial level below 7.5 percent and do not achieve an A1C treatment goal after about three months on single therapy, often metformin.3,[4] In addition, dual or triple therapy is recommended as first-line therapy in asymptomatic patients with an initial A1C level above 9 percent.3

Studies have demonstrated that administration of Invokamet results in the same levels and effects of canagliflozin and metformin in the body as co-administration of corresponding doses of both drugs as individual tablets. Canagliflozin works with the kidneys to help adults with type 2 diabetes lose some sugar through the process of urination, and metformin decreases the production of glucose in the liver and improves the body's response to insulin. Invokamet should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.1

Invokamet is available in four dose strengths, in tablets containing canagliflozin 50 milligrams (mg) or 150 mg, and metformin 500 mg or 1000 mg. The recommended dosing is twice daily. The prescribing information for Invokamet also contains a boxed warning for lactic acidosis, a rare, but serious complication that can occur due to metformin accumulation.1

“The available doses of Invokamet allow physicians to tailor therapy for individual patient needs and offer an alternative for people living with type 2 diabetes who may be able to reduce the number of pills they take each day,” said Paul Burton, M.D., Ph.D., Vice President, Medical Affairs, Janssen. “This expansion marks an important milestone as we continue to study Invokamet and INVOKANA®—the number-one prescribed SGLT2 inhibitor with more than 8 million prescriptions to date—for the treatment of type 2 diabetes.”

Phase 3 Study Supports Expanded Indication

The expanded indication for Invokamet was based largely on a 26-week, double-blind, active-controlled, multicenter Phase 3 study in 1,186 adults with type 2 diabetes inadequately controlled with diet and exercise, and who had not been treated previously with any glucose-lowering medications. The participants were assigned randomly to one of five treatment groups: metformin hydrochloride extended release (MET), canagliflozin 100 mg (CANA100), canagliflozin 300 mg (CANA300), canagliflozin 100 mg + MET (CANA100/MET), or canagliflozin 300 mg + MET (CANA300/MET). The mean baseline A1C across all groups was 8.8 percent. The primary endpoint was the change in A1C. A report on the study findings was published in Diabetes Care in March 2016.[5]

After 26 weeks, participants in the CANA100/MET and CANA300/MET groups had significantly greater decreases in A1C compared to those in the CANA100, CANA300 and MET groups: 1.77 percent and 1.78 percent vs. 1.37 percent, 1.42 percent and 1.3 percent, respectively (p-values for all differences between the combination therapies vs. individual therapies less than 0.001). Additionally, significantly more participants in the CANA100/MET and CANA300/MET groups compared to the MET group achieved the goal of reducing A1C to less than 7 percent: 47 percent and 51 percent vs. 38 percent, respectively (p less than 0.05 for both combination groups vs. MET).1

Other Phase 3 Studies of Canagliflozin-Metformin Therapy

The co-administration of canagliflozin—INVOKANA®—and metformin has been evaluated in six other Phase 3 clinical studies that enrolled 4,732 patients with type 2 diabetes and who were already taking glucose-lowering medications. The studies showed that the combination of INVOKANA® and metformin lowered blood sugar and, in pre-specified secondary endpoints, was associated with significant reductions in body weight and systolic blood pressure.

In two studies comparing INVOKANA® plus metformin to current standard treatments plus metformin—one studying sitagliptin and the other studying glimepiride—INVOKANA® dosed at 300 mg provided greater reductions in A1C levels and body weight than either comparator. The overall incidence of adverse events was similar with INVOKANA® and the comparators.

Results from the Phase 3 studies showed that INVOKANA® was generally well tolerated, and the most common adverse events include genital yeast infections, urinary tract infections, and changes in urination. The most common adverse reactions due to initiation of metformin, as noted in the prescribing information for that medication, are diarrhea, nausea, vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache. Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use. INVOKANA® can increase the risk of hypoglycemia when combined with insulin or a medication that increases insulin levels (e.g., a sulfonylurea). Therefore, a lower dose of insulin or insulin-raising medication may be required to minimize the risk of hypoglycemia when used in combination with Invokamet.

About Type 2 Diabetes

Of the approximately 29 million people who have diabetes in the United States, 90 to 95 percent of them have type 2 diabetes, which is chronic and affects the body's ability to metabolize sugar (glucose), and is characterized by the inability of pancreatic beta cell function to keep up with the body's demand for insulin

Metformin can reduce risk of open-angle glaucoma in people with diabetes

In continuation of my update on metformin

Taking the medication metformin hydrochloride was associated with reduced risk of developing the sight-threatening disease open-angle glaucoma in people with diabetes, according to a study published online by JAMA Ophthalmology.

Medications that mimic caloric restriction such as metformin can reduce the risk of some late age-onset disease. It is unknown whether these caloric mimetic drugs affect the risk of age-associated eye diseases such as macular degeneration, diabetic retinopathy, cataract or glaucoma.

Researcher Julia E. Richards, Ph.D., of the University of Michigan, Ann Arbor, and co-authors examined metformin use and the risk of open-angle glaucoma (OAG) using data from a large U.S. managed care network from 2001 through 2010.

Of 150,016 patients with diabetes, 5,893 (3.9 percent) developed OAG. Throughout the study period, 60,214 patients (40.1 percent) filled at least one metformin prescription; 46,505 (31 percent) filled at least one sulfonylurea prescription; 35,707 (23.8 percent) filled at least one thiazolidinedione prescription; 3,663 (2.4 percent) filled at least one meglitinide prescription; and 33,948 (22.6 percent) filled at least one insulin prescription. Some patients filled prescriptions for multiple medications.

Metformin can reduce risk of open-angle glaucoma in people with diabetes

FDA Approves Jentadueto ((linagliptin/metformin hydrochloride)).....

In continuation of my update on linagliptin and metformin hydrochloride

U.S. Food and Drug Administration (FDA) has approved Jentadueto (linagliptin/metformin hydrochloride) tablets, a new tablet combining the dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, and metformin. Jentadueto provides a new, single-tablet treatment option, taken twice-daily, for patients who need to control their blood sugar. Linagliptin (5 mg, once-daily) is marketed in the U.S. as Tradjenta (linagliptin) tablets....

More...

FDA Approves Jentaduet ((sitagliptin and metformin hydrochloride (HCl) )...

In continuation of my update on sitagliptin and metformin hydrochloride (HCl)

U.S. Food and Drug Administration (FDA) approved JANUMET^® XR    ((sitagliptin and metformin hydrochloride (HCl) ) extended-release) tablets, a new treatment for type 2 diabetes that combines sitagliptin, which is the active component of JANUVIA^® (sitagliptin), with extended-release metformin. JANUMET XR provides a convenient once-daily treatment option for healthcare providers and patients who need help to control their blood sugar.

More..

Metformin helps dieting teens to lose weight....

We know that Metformin  (see structure), is a  biguanide hypoglycemic  agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. Metformin's pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. In my earlier blogs, I have covered the recent (findings)  updates on metformin.

Now researchers  lead by Dr. Darrell Wilson (from Division of Pediatric Endocrinology and Diabetes, Stanford University)  have found that metformin appears to help overweight teenagers lose weight when combined with a program designed to help them change their lifestyle habits.

As per the claim by the authors though metformin hydrochloride is  used as a primary or adjunctive treatment in obese  nondiabetic adolescents there are limited short-term data to support this therapy  and also it is unclear whether any observed effects of metformin on body mass index. Therefore  the researchers conducted a 48-week randomized, double-blind, placebo-controlled trial of extended-release (XR) metformin therapy in nondiabetic obese adolescents  followed by a 48-week monitoring period after completion of treatment.

Researchers found that the addition of metformin to a lifestyle change intervention for a period of 12 months resulted in a significant improvement of BMI regardless of baseline fasting insulin levels, that persisted for 12 to 24 weeks after cessation of drug treatment. The mean (SE) reduction in BMI of –1.1 (0.5) at 1 year was comparable with that observed in other randomized controlled trials of metformin treatment in obese adolescents, although these randomized controlled trials involved shorter treatment duration (about 6 months), targeted obese children with additional diabetes risks, and had smaller sample sizes.

The mechanisms of action for these effects have not fully been elucidated but may involve beneficial effects on carbohydrate and lipid metabolism, mediated through adenosine monophosphate kinase.

Researchers conclude that  "metformin  in combination with lifestyle modification, had a small but statistically significant effect to reduce BMI in obese adolescents; this effect waned within 12 to 24 weeks of discontinuing metformin treatment". These results indicate that metformin may have an important role in the treatment of adolescent obesity. Longer-term studies will be needed to define the effects of metformin treatment on obesity-related disease risk in this population....

Ref : http://archpedi.ama-assn.org/cgi/content/full/164/2/116?home