Effects On The Inflammatory Pathway
The benefits of metformin on macrovascular complications of diabetes, separate from its conventional hypoglycemic effects, may be partially explained by actions beyond glycemic control, particularly by actions associated with inflammatory and atherothrombotic processes . Metformin can act as an inhibitor of pro-inflammatory responses through direct inhibition of NF-kB by blocking the PI3KAkt pathway. This effect may partially explain the apparent clinical reduction of cardiovascular events not fully attributable to metformins anti-hyperglycemic action .
Some studies also point to a modest effect on inflammatory markers in subjects with IGT in T2DM while others have found no effect at all .
Clinical Diagnosis Of Type 2 Diabetes
Diabetes may be identified in low-risk individuals who have spontaneous glucose testing during routine primary clinical care, in individuals examined for diabetes risk assessment, and in frankly symptomatic patients. Early diagnosis of T2DM can be accomplished through blood tests that measure PG levels. FPG is the most common test to detect diabetes: a level of 126 mg/dL or 7.0 mmol/L confirmed by repeating the test on another clinic visit effectively diagnoses the disease. This test requires fasting for at least the previous 8 h and generates enhanced reliability when blood is drawn in the morning. Another criterion is the 2 h PG of 200 mg/dL or 11.1 mmol/L in a patient presenting with the traditional symptoms of diabetes such as polyuria, polydipsia, and/or unexplained weight loss. A positive 2-h OGTT will show a PG level of 200 mg/dL or 11.1 mmol/L after a glucose load containing 75 g of glucose solution in water. Two-hour PG OGTT is not commonly used in the clinic because, although it is more sensitive than FPG test, it is less convenient and more expensive for patients. Additionally, this test holds less relevance in routine follow-ups after confirmed diagnosis of diabetes is obtained.
What Is The Trial Testing
This study will enroll 807 participants with type 2 diabetes and chronic kidney disease to compare the safety and efficacy of combining finerenone and empagliflozin versus using each medicine separately.
Participants will be randomly assigned to receive either:
Finerenone and empagliflozin
Finerenone and placebo
Empagliflozin and placebo
The primary goal of the study is to see if the combination therapy of finerenone and empagliflozin has better results on the kidney than either drug individually. To evaluate this, the level of protein in your urine and kidney function will be measured.
Additionally, the study team will:
collect blood and urine samples
do a physical examination, including height and weight
check your heart health by using an electrocardiogram
monitor your blood pressure
ask questions about how you are feeling and any adverse events
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Type 2 Diabetes: Which Medication Is Best For Me
- By Samar Hafida, MD, Contributor
If you are living with type 2 diabetes, you certainly are not alone. One in 10 people in the US has diabetes, according to the CDC. However, despite considerable progress in diabetes treatment over the past 20 years, fewer than half of those with diabetes actually reach their target blood sugar goal.
In part, this may be because doctors can be slow to make changes to a patients treatment plan, even when a patients treatment goals are not being met. One reason for this may be the overwhelming number of medications currently available. And yet, waiting too long to adjust treatment for type 2 diabetes can have long-lasting negative effects on the body that may raise the risk of heart and kidney disease and other complications.
Metformin In Combination Therapy
Although monotherapy with an oral hypoglycemic agent is often initially effective, glycemic control deteriorates in most patients which requires the addition of a second agent. Currently, marketed oral therapies are associated with high secondary failure rates . Combinations of metformin and insulin secretagogue can reduce HbA1c between 1.5% to 2.2% in patients sub-optimally controlled by diet and exercise .
The optimal second-line drug when metformin monotherapy fails is not clear. All noninsulin antidiabetic drugs when added to maximal metformin therapy are associated with similar HbA1c reduction but with varying degrees of weight gain and hypoglycemia risk. A meta-analysis of 27 randomized trials showed that thiazolidinediones, sulfonylureas, and glinides were associated with weight gain glucagon-like peptide-1 analogs, glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors were associated with weight loss or no weight change. Sulfonylureas and glinides were associated with higher rates of hypoglycemia than with placebo. When combined with metformin, sulfonylureas and alpha-glucosidase inhibitors show a similar efficacy on HbA1c .
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Metformin And Heart Failure
The risk of developing cardiac heart failure in diabetic individuals nearly doubles as the population ages . DM and hyperglycemia are strongly implicated as a cause for the progression from asymptomatic left ventricular dysfunction to symptomatic HF, increased hospitalizations for HF, and an overall increased mortality risk in patients with chronic HF . Despite all its benefits, metformin is contraindicated in patients with heart failure due to the potential risk of developing lactic acidosis, a rare but potentially fatal metabolic condition resulting from severe tissue hypoperfusion . The US Food and Drug Administration removed the heart failure contraindication from the packaging of metformin although a strong warning for the cautious use of metformin in this population still exists .
Several retrospective studies in patients with CHF and diabetes reported lower risk of death from any cause , lower hospital readmissions for CHF , and hospitalizations for any cause . A recent review concluded that CHF could not be considered an absolute contraindication for metformin use and also suggest its protective effect in reducing the incidence of CHF and mortality in T2DM . This protective effect may due to AMPK activation and decrease in cardiac fibrosis .
Targeting The Incretin/glucagon Systems
2.3.1. Dual Agonists
The design of GLP-1 and glucagon dual agonist has been explored, as well.
Glucagon is a hormone, which participates with insulin in glycemic homeostasis and, while remaining unclear whether low glucose levels directly stimulate glucagon release, it is a fact that T2DM patients suffer from hyperglucagonemia , an excess of glucagon secretion, possibly as a result of alpha cell insulin resistance.
Glucagon can be utilized therapeutically as a satiety factor, which also increases energy expenditure and weight loss . Since the incretin hormones and glucagon have some overlapping functions, their combined use could lead to synergistic effects on diabetes and related metabolic diseases .
Nevertheless, several studies also verified that acute co-infusion of low doses of GLP-1 and glucagon significantly reduced food intake and increased energy expenditure and this effect was achieved with peptide infused alone as well.
In addition, they have similar peptide sequences at the N-terminal region that allow the development of single-sequence multi-receptor agonists.
Structure of glucagon, GLP-1 and chimeric peptides. Amino acid sequence and structure of glucagon and GLP-1 chimera. Underlined residues indicate site of lactam formation. Helical wheel representation of glucagon, GLP-1 and chimeric peptide showing residues 1229.
Amino acid sequences of glucagon, the incretin hormones, and triagonist.
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What Are The Best Drugs To Treat Diabetes
Here are the Top 10 medications in terms of efficacy for lowering A1C and blood sugar levels.
Diabetes is a serious condition that is brought on by decreased insulin secretion from the pancreas and diminished insulin sensitivity in the muscle cells. It is characterized by excessive urination, extreme thirst, high blood sugar, and increased appetite.1
There are a number of medications on the market to help manage this condition, but the following are the top 10 in terms of showing efficacy in lowering A1C and blood sugar levels.
Patients with type 1 diabetes must be treated with insulin, as the beta cells in their pancreas no longer produce it. Insulin plays a vital role in glucose uptake and is required by the muscle and adipose tissue.2 However, insulin is not solely for patients with T1D those with type 2 diabetes may also be placed on insulin but generally only after failing to reach glycemic targets upon being placed on multiple oral agents for some time. Patients with diabetes typically receive multiple injections per day, including bolus insulin administered before meals and the long-acting basal insulin that lowers blood sugar levels over time. Insulin is classified as a high-risk drug because it can cause patients to experience hypoglycemia, but the benefits of this treatment surely outweigh the risks.2
The most common insulins I see prescribed in my daily practice are Basaglar and NovoLog .
Sugar Raises Blood Pressure
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Learn More About Accessing Intelligence For Your Therapy Area
Healthcare Insights are developed with healthcare commercial intelligence from the Definitive Healthcare platform.
Pharmaceutical companies developing new type 2 diabetes drugs or combination-use drugs can accelerate pre-launch planning with up-to-date and comprehensive visibility into patient and brand market share for a therapy area.
Metformin In The Management Of Adult Diabetic Patients
Current guidelines from the American Diabetes Association/European Association for the Study of Diabetes and the American Association of Clinical Endocrinologists/American College of Endocrinology recommend early initiation of metformin as a first-line drug for monotherapy and combination therapy for patients with T2DM. This recommendation is based primarily on metformins glucose-lowering effects, relatively low cost, and generally low level of side effects, including the absence of weight gain .
Metformins first-line position was strengthened by the United Kingdom Prospective Diabetes Study observation that the metformin-treated group had risk reductions of 32% for any diabetes-related endpoint, 42% for diabetes-related death , and 36% for all-cause mortality compared with the control group. The UKPDS demonstrated that metformin is as effective as sulfonylurea in controlling blood glucose levels of obese patients with type 2 diabetes mellitus . Metformin has been also been shown to be effective in normal weight patients .
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What Is The Quickest Thing To Take To Bring Your Blood Sugar Down
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Most Diabetes Medications Effectively Lower Blood Sugar
The blood sugar goal for most adults with diabetes is an A1C of below 7%. In many people, diet and exercise are not enough to reach this goal, and one or more medications may be needed. Metformin is a tried and tested medicine that has been used for many decades to treat type 2 diabetes, and is recommended by most experts as first-line therapy. It is affordable, safe, effective, and well tolerated by most people.
When metformin does not adequately control blood sugar, another medication must be added. It is at this point that doctors and patients must choose among the many drugs and drugs classes available to treat type 2 diabetes. In general, for people who are at low risk of heart disease or have no history of diabetic kidney disease, most diabetes medications that are added to metformin effectively reduce blood sugars and can lower A1C to under 7%.
So, how to choose a medication? Each person with diabetes has their own goals, needs, and preferences. Before choosing a medicine, it is important to ask some relevant questions: Is my blood sugar at goal? Is this medicine affordable? Do I have heart or kidney disease? What are the side effects? Is it a pill or injection, and how often is it taken?
Regardless of which treatment is selected, the American Diabetes Association Standards of Care recommends reassessment of diabetes control every three to six months, followed by modifications to treatment if needed.
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Why Is This New Trial Important
Diabetes is one of the most common causes of chronic kidney disease in adults, with around 1 in 3 people with diabetes also living with CKD. It is estimated that as many as 40% of people with diabetes may develop CKD during their lifetimes. To learn more about chronic kidney disease, read our article, Chronic Kidney Disease: The Hidden Complication.
Finerenone is a drug that was approved by the FDA in July 2021 to treat chronic kidney disease in people with type 2 diabetes. Empagliflozin is an SGLT-2 inhibitor that has been proven to lower blood glucose levels for people with diabetes. It also reduces the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure and reduces the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease. Testing how these medications work together could lead to a more convenient option that combines both finerenone and empagliflozin.
Trial Length: 6 months
Trial Locations: This is a multicenter, worldwide study with 131 locations across the United States, Belgium, Canada, Germany, Japan, Italy, Spain, and Taiwan. See a list of all participating locations here.
Metformin Use In Childhood And Adolescence
Type 2 diabetes mellitus has dramatically increased in children and adolescents worldwide to the extent that has been labeled an epidemic . Before 1990, it was a rare condition in the pediatric population by 1999, the incidence varied from 8% to 45%, depending on geographic location, and was disproportionally represented among minority groups . There are few studies of metformin use in the pediatric population. Most of them are of short duration and heterogeneous designs.
The beneficial role of metformin in young patients with type 2 diabetes has been demonstrated in a randomized, controlled trial which showed a significant decrease in fasting blood glucose, HbA1c, weight, and total cholesterol. The most frequently reported adverse events were abdominal pain, diarrhea, nausea/vomiting, and headaches. There were no cases of clinical hypoglycemia, lactic acidosis, or clinically significant changes in physical examinations . When compared to glimepiride , metformin lowered HbA1c to < 7%, similar to glimepiride, but was associated with significantly less weight gain. A total of 42.4% and 48.1% of subjects in the glimepiride and metformin groups, respectively, in the intent-to-treat population achieved A1C levels of < 7.0% at week 24 .
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Cautions With Other Medicines
There are some medicines that may increase the effects of empagliflozin.
This can make you more likely to get side effects.
Tell your doctor if you are taking any of these medicines:
- medicines that make you pee more , like furosemide â these can increase your risk of dehydration and lower your blood pressure
- high blood pressure medicines
- other medicines that can lower your blood pressure â including some antidepressants, nitrates , baclofen , tamsulosin , or co-careldopa or levodopa
- medicines that cause low blood sugar, such as insulin or gliclazide â your doctor may lower your dose of these other medicines to prevent hypos
Most Utilized Drugs To Treat Type 2 Diabetes
Diabetes is on the rise in the United States. Experts project the prevalence of this chronic disease will affect more than 54.9 million individuals in the U.S. by 2030. As a result, we can expect to see annual medical and societal costs top $622 billion by 2030.
Type 2 diabetes is the most common form of diabetes, affecting 90-95% of diabetes patients.
Using Definitive Healthcares Passport Express-Type 2 Diabetes Edition, we analyzed type 2 diabetes drugs by patient share for 2020-21 vs. 2021-2022. The table below lists the top type 2 diabetes drugs by patient share. Since some patients receive a combination of treatments , the percentages in the columns add up to more than 100%.
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