Evaluation of Fenugreek Seed Extract In Type- 2 Diabetes: An Add-On Study
Condition: Diabetes
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 4

Summary: 
      Trigonella Foenum-Graecum, commonly known as Fenugreek, is a plant that has been extensively
      used as a source of anti-diabetic compounds Fenugreek is traditionally used in India,
      especially in the Ayurvedic and Unani systems.

      Preliminary animal and human trials suggest possible hypoglycemic and anti-hyper lipidemic
      properties of Fenugreek seed powder, when taken orally. Fenugreek seeds contain 50% fiber
      (30% soluble fiber and 20% insoluble fiber) that can slow the rate of post-prandial glucose
      absorption. This may be a secondary mechanism for the hypoglycemic effect.
    

Detailed description: 
      Diabetes mellitus is a complex heterogeneous group of metabolic conditions characterized by
      increased levels of blood glucose due to impairment in insulin action and/or insulin
      secretion. Diabetes is a condition primarily defined by the level of hyperglycemia giving
      rise to risk of microvascular damage (retinopathy, nephropathy and neuropathy). It is
      associated with reduced life expectancy, significant morbidity due to specific diabetes
      related Microvascular complications, increased risk of macrovascular complications (ischemic
      heart disease, stroke and peripheral vascular disease), and diminished quality of life.Type 2
      diabetes mellitus (T2DM) is the most common form of diabetes in humans and results from a
      combination of genetic and acquired factors that impair -cell function and tissue insulin
      sensitivity.

      The WHO has put the number of persons with diabetes worldwide at approximately 170 million.
      The prevalence of diabetes mellitus has risen dramatically over the past 20 years, and the
      number of people with diabetes is expected to reach 366 million by 2025. The prevalence of
      type 2 diabetes mellitus is expected to grow even more rapidly in the future. There is also
      considerable geographic variation in the incidence of T2DM, and countries like India are fast
      emerging as ''diabetes hot spots". About 5-10% of the total health care budget has been used
      for T2DM in many countries.

      Reduced pancreatic β-cell functional mass in diabetes, and other categories of glucose
      intolerance, has been described by several authors, and decreased islet and/or -cell volume
      in the pancreas of type 2 diabetic patients has been consistently reported. In addition,
      studies conducted in patients, and isolated islets, have shown both quantitative and
      qualitative defects of glucose-stimulated insulin secretion.

      The ideal antidiabetic agent should normalize plasma glucose, minimize side effects, and
      prevent development of micro- and macrovascular complications. Obviously no such agent is
      available, nor is it likely to be available in the near or medium-term future.

      Current treatments and treatment regimens include combinations of oral antidiabetic drugs
      (OADs), antihypertensive medications, and antidyslipidemic agents, but these have been less
      than successful in managing their respective disease targets with clinical goals. Measures
      such as screening and intensive life-style modification can help to delay the onset of
      diabetes in at-risk individuals, and stringent glycemic control with pharmacotherapy may
      improve outcomes. To manage the type 2 diabetes epidemic effectively, however, agents that
      can effectively and durably controls glycemia while providing pleiotropic benefits (e.g.
      blood pressure reduction) are required.

      The landmark Diabetes Control and Complications Trial and the United Kingdom Prospective
      Diabetes Study (UKPDS) have convincingly demonstrated that normalizing glycosylated
      hemoglobin (HbA1C) levels in individuals with diabetes can reduce diabetes-related
      cardio-vascular (CV) morbidity and mortality as well as the incidence and progression of
      micro vascular complications.

      HbA1C concentration is an accurate predictor of risk for such complications, with a desirable
      goal of 7.0% or less. In the clinical setting, measurement of HbA1C assesses longer-term
      glycemic control among individuals with diabetes.

      A range of therapeutic agents exist for the treatment of type 2 diabetes. Metformin, a
      biguanide, is a commonly prescribed oral anti diabetic drug; American Diabetes Association
      (ADA)/European Association for the Study of Diabetes (EASD) guidelines recommend metformin as
      initial pharmacotherapy for type 2 diabetes, with an expected reduction in HbA1C of between
      1.0% and 2.0%. In their recommendations, both the ADA and the International Diabetes
      Foundation support metformin as initial pharmacotherapy for type 2 diabetes.

      However, Metformin is associated with increased CV risk and lactic acidosis, and it is
      contraindicated in patients with heart failure or impaired renal function. Metformin
      monotherapy has also been associated with diarrhea in approximately 50% of patients and
      nausea or vomiting in 25% of patients.

      Sulfonylurea's (SUs) e.g., glimepiride have long been an effective and low-cost mainstay of
      type 2 diabetes therapy; as with metformin, SU monotherapy can be expected to reduce HbA1C by
      1.0% to 2.0%. SUs are a common alternative or add-on to metformin and act by stimulating
      pancreatic beta-cell insulin secretion in a glucose-independent manner. Weight gain is a
      common adverse effect of SU therapy, as is an increased risk of hypoglycemia, particularly in
      the elderly and in patients with worsening renal function.

      Thiazolidinedione (TZD) monotherapy has been associated with HbA1C reductions of between 0.5%
      and 1.4%. TZDs have beneficial effects on CV markers, including lipid levels (particularly
      triglycerides and HDL-Cholesterol), blood pressure, inflammatory mediators, endothelial
      function, and fibrinolytic status. However, weight gain and increased risk of edema and heart
      failure are frequent adverse effects, particularly when TZDs are used in combination with
      insulin.

      Alpha-glucosidase inhibitors, such as acarbose, act as competitive inhibitors of the alpha
      glucosidases, thereby delaying glucose absorption. This effect on glucose uptake decreases
      glucose peak and insulin response postprandially and moderately lowers fasting plasma glucose
      levels and HbA1C, but gastrointestinal adverse effects and the requirement for three times
      daily dosing may inhibit adherence to therapy. Monotherapy with alpha-glucosidase inhibitors
      have been associated with HbA1C reductions of between 0.5% and 0.8%, with no weight gain.

      Glinide (i.e., repaglinide, nateglinide) monotherapy has been reported to reduce HbA1C by
      between 0.5% and 1.5%. The rapid onset of action of glinides necessitates three times daily
      dosing, and they have been associated with hypoglycemia. Weight gain has been reported with
      glinide therapy (between 0.7 and 1.8 kg).

      Insulin, either alone or in combination with other agents, most commonly metformin, is an
      effective option for restoring normoglycemia, especially when administered early in the
      disease course. The disadvantages of insulin therapy are weight gain and an increased risk of
      hypoglycemia. Insulin has not been observed to have clinically relevant effects on either
      blood pressure or lipids.

      In addition to devising the most appropriate pharmacotherapeutic regimen for the patient with
      type 2 diabetes, patient management is also of critical importance and is best handled by a
      medical care team including the physician, the pharmacist, the dietitian, and a diabetes
      education specialist. Ideally, a diabetes care plan should be developed with input from all
      medical care team practitioners and the patient. Incretin-based therapies, which include the
      glucagon-like peptide (GLP)-1 receptor agonist's exenatide and exenatide Long acting release
      (LAR), and liraglutide and the Dipeptidyl peptidase-4 (DPP-4) inhibitors sitagliptin,
      vildagliptin, and saxagliptin represent a new class of antidiabetic drugs. Data suggest an
      equal or potentially greater efficacy of incretin-based therapies to lower HbA1C compared
      with other antidiabetic therapies, with a low risk of hypoglycemia. Other benefits include
      weight reduction (GLP-1 receptor agonists) or weight neutrality (DPP-4 inhibitors).GLP-1
      receptor agonists have recently been added to the ADA/EASD treatment algorithm as a tier 2
      alternative to the addition of SUs or basal insulin in patients not adequately controlled on
      metformin plus lifestyle modification.

      The OADs are able, for a time, to reduce A1C but do not correct all the metabolic and
      glucoregulatory dysfunctions involved in type 2 diabetes pathophysiology. As a result, HbA1C
      goals become more difficult to maintain and a significant glycemic burden accumulates,
      increasing the risk of CV diseases. The treatment of co morbid conditions, particularly
      hypertension, may also impede achieving and maintaining glycemic goals. Difficulties in
      maintaining long-term glycemic control with currently available antidiabetic therapies have
      led to the need for additional treatments that can be used as monotherapy or combined safely
      with existing agents and that may target more of the underlying pathologies of type 2
      diabetes.

      Although traditional treatments and treatment combinations are initially successful at
      lowering HbA1C, they are unable to restore normoglycemia over the long term. Recent data that
      suggest the mean time to secondary failure on OADs (a therapeutic event necessitating the
      addition of another agent or insulin) may be as short as 1.3 years.

      The primary goal in the treatment of patients with type 2 diabetes is the maintenance of
      beta-cell function, the decline of which is the major reason for impairment in glucose
      tolerance over time. Consequently, therapies that arrest progressive beta-cell deterioration
      while restoring and maintaining normoglycemia will be required. New therapies are needed that
      will also minimize weight gain and correct dyslipidemia without compromising improvements in
      glycemic control.

      The Investigational Agent Trigonella Foenum Graecum, commonly known as Fenugreek, is a plant
      that has been extensively used as a source of antidiabetic compounds, from its seeds, leaves
      and extracts in different model systems. Fenugreek is traditionally used in India, especially
      in the Ayurvedic and Unani systems.Preliminary animal and human trials suggest possible
      hypoglycemic and anti-hyperlipidemic properties of fenugreek seed powder taken orally.
      Fenugreek seeds contain 50% fiber (30% soluble fiber and 20% insoluble fiber) that can slow
      the rate of post-prandial glucose absorption. This may be a secondary mechanism for the
      hypoglycemic effect.
    

Intervention name(s): Fenugreek seeds extract; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Fenugreek seed extract 500mg, BD; Placebo capsule containing Dicalcium Phosphate 500mg, BD
Other intervention name(s): Fenfuro
Intervention MeSH terms: Fenugreek seed meal
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Type-2 Diabetic; HbA1c; FBS; PPBS; C-peptide