Dulaglutide is marketed by the brand name "TRULICITY" worldwide by Eli Lilly. It is a long-acting GLP-1 agonist that increases endogenous insulin secretion, reduces glucagon levels, and delays gastric emptying. It is used as an adjunct to exercise and diet for the treatment of Diabetes Mellitus Type 2 in combination with metformin, sulfonylureas, or insulin. Concomitant use with DPP-4 inhibitors (Januvia, Janumet, Galvus, Galvusmet) and other parenteral or oral GLP-1 analogs should be avoided.

Dulaglutide Cardiovascular outcomes:

Compared to placebo in one study, patients in the dulaglutide group had a reduction in the primary outcomes defined as the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes). However, the all-cause mortality did not differ between the groups [Ref].

Dulaglutide and Semaglutide:

Dulaglutide and semaglutide are weekly administered GLP-1 agonists that were compared in the SUSTAIN 7 trial. Compared to dulaglutide (Trulicity), Semaglutide (Ozempic) was superior in terms of glycemic control and weight reduction at low and high doses [Ref]. Dulaglutide was studied in the REWIND trial and it was associated with reduced composite renal outcomes [Ref].

Trulicity vs metformin, sitagliptin, exenatide, and insulin glargine:

The AWARD 3 trial compared dulaglutide with the active comparators that included metformin, Sitagliptin, Exenatide, and Insulin glargine. Compared to the above-mentioned active comparators, dulaglutide was more effective in reducing weight and had better glycemic control. It was equally effective as Liraglutide [Ref]. Dulaglutide also improved the islet cell functions as measured by the HOMA model compared to metformin. Compared to Insulin Glargine in patients with mild to moderate kidney impairment, dulaglutide was safe and effective in improving glycemic control [Ref].

Dulaglutide 0.75 mg in Type 1 Diabetes Mellitus and Type 2 Diabetic patients with absolute insulin deficiency:

The safety and efficacy of Dulaglutide in a dose of 0.75 mg were investigated in patients with islet-antibody positive T1DM and T2DM patients lacking Beta-cell function. Dulaglutide reduced the HbA1C effectively when added to background insulin. However, it did not affect the C-peptide levels. The efficacy of the dulaglutide was thought to be due to a reduction in the glucagon levels, delayed gastric emptying, and an improvement in insulin sensitivity [Ref].

Foods to avoid with Trulicity:

Dulaglutide, like other GLP-1 analogs (Semaglutide and Liraglutide) and DPP-4 inhibitors (Sitagliptin, Vildagliptin, and Linagliptin) delays gastric emptying. It may impair the absorption of essential medicines like levothyroxine. Patients should also be instructed to reduce oily foods as it may precipitate biliary disease especially in patients with gall stones.

Adult dose:

(Trulicity) Dulaglutide dose in the treatment of Type 2 diabetes mellitus:

• 0.75 mg subcutaneously once a week initially.
• The dose may be increased to 1.5 mg once a week if the target blood sugars are not achieved.
• The maximum dose is 1.5 mg/week.

What if the dose is missed?

In case of a missed dose, it should be administered as soon as possible and within three days after the missed dose. If more than 3 days have lapsed, it should be administered on the scheduled day.

Dose in children:

Trulicity Dose in Children:

It is not recommended for use in children.

Pregnancy Risk Category: C

• Studies on animals have shown that fetal health can be seriously affected.
• Manufacturers recommend other treatments such as insulin and metformin.
• Patients with diabetes should plan their pregnancy.
• Before conception, blood sugars must be within the recommended ranges.
• Uncontrolled blood sugar levels can lead to congenital malformations or adverse maternal outcomes.

Use while breastfeeding

• It is unknown if the drug will be excreted into breastmilk.
• Manufacturers recommend that you weigh the risks to your infant and the benefits for the mother when treating her.

Dose in kidney disease:

• In the case of renal impairment, it should be used cautiously.
• However, the manufacturer has not suggested any adjustments to the dose for patients with kidney disease.

Dose in liver disease:

• You should use it with caution if you have a hepatic impairment.
• However, the manufacturer has not suggested any adjustments to the dose for patients with liver disease.

(Trulicity) Dulaglutide Side Effects (Common):

• Gastrointestinal:

  • Nausea
  • Diarrhea
  • Vomiting

Less Common Side Effects of Trulicity (Dulaglutide):

• Cardiovascular:

  • Sinus Tachycardia
  • Prolongation P-R Interval On ECG
  • First Degree Atrioventricular Block
  • Sustained Tachycardia

• Central Nervous System:

  • Fatigue

• Endocrine & Metabolic:

  • Hypoglycemia
  • Severe Hypoglycemia

• Gastrointestinal:

  • Abdominal Pain
  • Decreased Appetite
  • Dyspepsia
  • Constipation
  • Flatulence
  • Abdominal Distension
  • Eructation
  • Gastroesophageal Reflux Disease

• Immunologic:

  • Antibody Development

(Trulicity) Dulaglutide Contraindications:

• Severe allergic reactions to dulaglutide and any component of this formulation.
• A positive family history or personal history of medullary gland carcinoma (MTC).
• MEN - 2 (multiple Endocrine Neoplasia Syndrome type 2)
• Pregnancy
• Breastfeeding

Trulicity Warnings & Precautions

• Cardiovascular effects

  • Use of dulaglutide has been linked to an increase in cardiac arrhythmias.
  • It is common to experience cardiac problems such as tachycardia, prolongation in PR interval, and first degree AV block.
  • Preexisting conduction problems, structural heart disease, ischemic or ischemic heart disease and cardiomyopathies should not be treated with the drug.

• Hypersensitivity reactions

  • It can cause severe allergic reactions.
  • Angioedema and anaphylactic reactions can be signs of allergic reactions. These reactions require immediate treatment with adrenaline.
  • Patients who have had allergic reactions should not use the drug.
  • Patients allergic to GLP-1 analogs should be cautious. Cross-reactivity could occur.

• Pancreatitis

  • Like other GLP-1 analogs or DPP-4 inhibitors, Dulaglutide has been linked to an increased risk for pancreatitis.
  • Pancreatitis symptoms such as nausea, vomiting, abdominal pain and nausea should be reported to the doctor immediately.
  • Patients with pancreatitis must stop taking the medication.
  • If an alternative cause for pancreatitis is confirmed, reinitiation may be considered.
  • Patients with a history or pancreatitis should consider other anti-diabetic medications.

• Thyroid tumors: [US Boxed Warning]

  • Long-term dulaglutide use has been linked to thyroid malignancies, particularly C-cell tumors.
  • The association between medullary thyroid carcinoma and dulaglutide in humans is not well-known.
  • Any symptoms such as neck mass, dyspnea or hoarseness should be reported to the doctor.
  • Avoid thyroid medullary cancer in patients with a history of it or in their families.
  • Once a thyroid mass has been reported, patients should have their serum calcitonin levels checked.

• Gastrointestinal Disease:

  • Avoid the use of this drug in patients with diabetes, gastrointestinal problems, and those who have had recent surgery.

• Hepatic impairment

  • Patients suffering from liver disease should be cautious when taking the drug.

• Renal impairment

  • Patients who have a pre-existing kidney injury should not use it.
  • It has been associated with acute and chronic renal failure.
  • Patients with renal dysfunction experience severe gastrointestinal reactions, including nausea, vomiting, diarrhea, and other symptoms.
  • Patients suffering from GI upset may develop renal impairment.

Dulaglutide: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitor:

• Plasma glucose
• Glycated hemoglobin is measured every six months if blood sugars fall within the target ranges. It is measured every three months if they are not.
• Monitor renal function
• Pancreatitis can be characterized by abdominal pain, nausea, vomiting, and other symptoms.

How to administer Dulaglutide (Trulicity)?

• This should only be used subcutaneously. It should be subcutaneously administered to the abdomen (around and around the umbilicus), upper arms, or mid-thighs, just like insulin.
• Rotating the injection site each week is a good idea. The injection should be given once a week, on the same day every week, without any consideration for meals or the time of day.
• If the date of administration must change, there should be a minimum of three days between each dose.
• You can administer it with insulin, but avoid injections adjacent to insulin. It should not be combined with any injectable medicine.

(Trulicity MOA) Dulaglutide Mechanism of action:

• Dulaglutide (Glucagon-like peptide-1) is a human GLP-1 (Glucagon-dependent insulin secretion) agonist.
• It stimulates glucose-dependent insulin production, decreases glucagon secretion and delays gastric emptying.
• It is administered subcutaneously once a week with a bioavailability between 47 and 65%.
• It is converted to amino acids, and has a half life of approximately 5 days. It takes approximately 24 to 72 hours for the plasma concentration to reach its peak.

International brands:

Dulaglutide Brand Names (International):

• Trulicity

Injection Trulicity Price in the US:

• 0.75 mg/0.5 mL: $227.82
• 1.5 mg/0.5 mL: $227.82

Dulaglutide Brand Name in Pakistan:

• Trulicity

Trulicity Price in Pakistan:

Rs. 14000 approx per month (four injections)