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Science of BYETTA

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Mechanism of action

BYETTA: 5 key actions

Multiple actions of GLP-1 in glycemic regulation

<div class="content_txt intend_txt"><p class="subhead">BYETTA is not indicated for weight loss.</p>

<p class="smalltext">*Weight reduction was a secondary end point</p>

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BYETTA is not indicated for weight loss.

*Weight reduction was a secondary end point

Multiple glucoregulatory actions of BYETTA

BYETTA is not indicated for weight loss.

*Weight reduction was a secondary end point

BYETTA restores first-phase insulin response

  • In healthy individuals, robust insulin secretion, known as first-phase insulin response, occurs during the first 10 minutes following lV glucose administration
  • First-phase insulin response is characteristically absent in patients with type 2 diabetes and is an early indicator of beta-cell dysfunction
Pharmacodynamics chartPharmacodynamics chart

Abbreviations: T2D=type 2 diabetes; IV=intravenous

  • aPatients received an lv infusion of insulin for 6.5 hours (discontinued at [t] = -30 minutes) to normalize plasma glucose concentrations and a continuous lV infusion of either exenatide or saline for 5 hours beginning 3 hours prior to an lV bolus of glucose (0.3 g/kg over 30 seconds) at t=0 minutes.

Abbreviations: T2D=type 2 diabetes; IV=intravenous

  • At therapeutic plasma concentrations, BYETTA restored the early, first-phase insulin response to an lV bolus of glucose as well as increased the first-phase insulin secretion and second-phase insulin secretion in patients with type 2 diabetes


Pharmacodynamics: PPG profile

With BYETTA, reductions in PPG concentrations contribute to improvements in glycemic control.

Multiple glucoregulatory actions of BYETTA
PPG profile following a single dose of BYETTAPPG profile following a single dose of BYETTA
  • *Adult patients with type 2 diabetes treated with mecformin, sulfonylurea, or both were administered a single dose of BYETTA (mean dose, 7.8 mcg based on body weight) by subcutaneous injection.
  • Following a standardized meal, BYETTA® (exenatide) injection reduced elevated PPG excursions to a nearly flat profile in patients with type 2 diabetes
Clinical pharmacokinetics and dosing of BYETTA and insulin lispro
Clinical_Pharmacokinetics_Chart_mobile

Select Important Safety Information: Warnings and Precautions

  • Never Share a BYETTA Pen Between Patients: Pen-sharing poses a risk for transmission of blood-borne pathogens, even if the needle is changed.
  • Pancreatitis: Based on postmarketing data BYETTA has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. After initiation and dose increases of BYETTA, observe patients carefully for pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting). If pancreatitis is suspected, BYETTA should be discontinued promptly and should not be restarted if pancreatitis is confirmed.
  • Hypoglycemia: Increased risk of hypoglycemia when used in combination with a sulfonylurea (SU) or when used with a glucose-independent insulin secretagogues (eg, meglitinides). Clinicians may consider reducing the SU dose in patients receiving BYETTA to reduce the risk of hypoglycemia. When used with insulin, evaluate and consider reducing the insulin dose in patients at increased risk of hypoglycemia.
  • Folowing a standardized meal, BYETTA reduced elevated PPG excursions to a nearly flat profile in patients with type 2 diabetes

PPG plays a key role in overall glycemic control

Relative contribution of PPG and FPG to overall glycemic controlRelative contribution of PPG and FPG to overall glycemic control
  • Abbreviations: FPG, fasting plasma glucose; PPG, postprandial glucose.
  • Four-point plasma-glucose profiles (of patients with type 2 diabetes treated with diet alone or stable doses of metformin, sulfonylurea, or both [N = 290]) were used to determine relative contributions of PPG and FPG.
  • BYETTA was not included in this study.
  • As A1C levels decrease toward 7%, the relative contribution of PPG to overall A1C is higher aompared to fasting plasma glucose (FPG); alternately, FPG plays a greater role at higher A1C levels2

Select Important Safety Information: Warnings and Precautions

  • Renal Impairment: Should not be used in patients with severe renal impairment or end-stage renal disease. Use with caution in patients with renal transplantation or when initiating or escalating the dose in patients with moderate renal failure. Postmarketing reports of altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation.
  • Gastrointestinal Disease: Because exenatide is commonly associated with gastrointestinal adverse reactions, BYETTA is not recommended in patients with severe gastrointestinal disease (eg, gastroparesis).
  • Immunogenicity: Patients may develop antibodies to exenatide. In 3 registration trials, antibody levels were measured in 90% of patients, with up to 4% of patients having high-titer antibodies and attenuated glycemic response. If worsening of or failure to achieve adequate glycemic control occurs, consider alternative antidiabetic therapy.
  • Hypersensitivity: Postmarketing reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema). If this occurs, patients should discontinue BYETTA and other suspect medications and promptly seek medical advice.
  • Macrovascular Outcomes: No clinical studies establishing conclusive evidence of macrovascular risk reduction with BYETTA or any other antidiabetic drug.


Guidelines

Medical Guidelines

Medical guidelines include glucagon-like peptide-1 (GLP-1) receptor agonists as an option for glycemic control3,4

American Diabetes Association (ADA)

  • If basal insulin has been titrated to an acceptable fasting blood glucose level, but A1C remains above target, consider advancing to combination injectable therapy to cover postprandial glucose excursions. Options include adding a GLP-1 RA or mealtime insulin, consisting of 1 to 3 injections of rapid-acting insulin analog (lispro, aspart, or glulisine) administered just before eating2

American Association of Clinical Endocrinologists (AACE)

  • In patients who fail to achieve glycemic control with basal (long-acting) insulin, the AACE recommends treatment intensification for prandial control using non-insulin therapy such as a GLP-1 RA, SGLT-2 inhibitor or DPP-4 inhibitor, or treatment with prandial insulin3

2015 ADA recommendations for GLP-1 RA therapy4

ADA 2015 recommendations for GLP-1 therapyADA 2015 recommendations for GLP-1 therapy
  • Adapted from Inzucchi et al.
  • American Diabetes Association, Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach; Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes, American Diabetes Association, 2015. Copyright and all rights reserved. Material from this publication has been used with the permission of American Diabetes Association.
  • Abbreviations: GI, gastrointestinal; GLP-1-RA, glucagon-like peptide-1 receptor agonist; Hypo, hypoglycemia; SGLT2-I, sodium-glucose cotransporter 2 inhibitor; SU, sulfonylurea; TZD, thiazolidinedione.
  • *Consider starting at this stage when A1C is ≥9%.
  • Consider starting at this stage when blood glucose is ≥300 to 350 mg/dL (16.7-19.4 mmol/L) and/or A1C is ≥10% to 12%, especially if symptomatic or catabolic features are present, in which case basal insulin plus mealtime insulin is the preferred initial regimen.
  • Usually a basal insulin (Neutral Protamine Hagedorn, glargine, detemir, degludec).

aAdult patients with type 2 diabetes treated with metformin, sulfonylurea, or both were administered a single dose of BYETTA (mean dose, 7.8 mcg based on body weight) by subcutaneous injection.

Following a standardized meal, BYETTA reduced elevated PPG excursions to a nearly flat profile in patients with type 2 diabetes.

Select Important Safety Information: Warnings and Precautions

  • Never Share a BYETTA Pen Between Patients: Pen-sharing poses a risk for transmission of blood-borne pathogens, even if the needle is changed.
  • Pancreatitis: Based on postmarketing data BYETTA has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. After initiation and dose increases of BYETTA, observe patients carefully for pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting). If pancreatitis is suspected, BYETTA should be discontinued promptly and should not be restarted if pancreatitis is confirmed.
  • Hypoglycemia: Increased risk of hypoglycemia when used in combination with a sulfonylurea (SU) or when used with a glucose-independent insulin secretagogues (eg, meglitinides). Clinicians may consider reducing the SU dose in patients receiving BYETTA to reduce the risk of hypoglycemia. When used with insulin, evaluate and consider reducing the insulin dose in patients at increased risk of hypoglycemia.