What is the efficacy of injectable peptides, such as teriparatide (generic name) for osteoporosis or liraglutide (generic name) for type 2 diabetes, in a general population with no underlying medical conditions?

Efficacy of Injectable Peptides

Injectable peptides demonstrate robust efficacy for their approved indications: GLP-1 receptor agonists (like liraglutide) significantly reduce all-cause mortality and major adverse cardiovascular events in type 2 diabetes, while teriparatide substantially increases bone mineral density in osteoporosis patients. 1, 2

GLP-1 Receptor Agonists (e.g., Liraglutide)

Mortality and Cardiovascular Benefits

• GLP-1 receptor agonists reduce all-cause mortality compared to usual care (high certainty of evidence) and reduce major adverse cardiovascular events (MACE) with moderate to high certainty. 1

• Liraglutide specifically demonstrated a 13% reduction in the composite outcome of myocardial infarction, stroke, or cardiovascular death (HR 0.87; 95% CI 0.78–0.97) in the LEADER trial, which included 9,340 patients with type 2 diabetes at high cardiovascular risk. 1

• Cardiovascular death was reduced by 22% with liraglutide (HR 0.78; 95% CI 0.66–0.93) compared to placebo. 1

• The mortality benefit is particularly pronounced in patients with chronic kidney disease, where liraglutide showed significantly greater MACE risk reduction in those with eGFR <60 mL/min/1.73 m² compared to those with higher eGFR. 1

Glycemic Control and Weight Management

• GLP-1 receptor agonists achieve modest HbA1c reductions of approximately 0.4% when added to insulin therapy in type 1 diabetes, with weight reductions of approximately 5 kg. 1

• Injectable formulations demonstrate higher glucose-lowering efficacy compared to oral formulations, with semaglutide showing the greatest weight reduction potential among GLP-1 receptor agonists. 3

• In patients with overweight or obesity but without diabetes, semaglutide reduced cardiovascular death, MI, or stroke by 20% (HR 0.80; 95% CI 0.72–0.90) in the SELECT trial. 1

Renal Protection

• GLP-1 receptor agonists reduce albuminuria and slow eGFR decline, with evidence from cardiovascular outcomes trials including participants with eGFR as low as 15 mL/min/1.73 m². 1

• Meta-analysis of 8 cardiovascular outcomes trials showed GLP-1 receptor agonists significantly reduced risk for composite kidney disease outcomes including macroalbuminuria, eGFR decline, and progression. 1

Safety Profile

• The predominant adverse events are gastrointestinal: nausea, vomiting, diarrhea, and constipation, which are dose-dependent. 4

• Serious but rare risks include pancreatitis, gallbladder disease, and thyroid concerns. 4

• GLP-1 receptor agonists demonstrate less frequent serious adverse events and severe hypoglycemia compared to insulin or sulfonylureas (high certainty of evidence). 1

Clinical Caveat

• Rapid weight loss with GLP-1 agonists can trigger telogen effluvium (temporary hair loss), which may be mistaken for a direct drug effect. 4

• Nutritional deficiencies from reduced caloric intake or gastrointestinal side effects may contribute to hair loss and should be monitored. 4

Teriparatide for Osteoporosis

Bone Mineral Density Improvements

• Teriparatide increases lumbar spine BMD by 9.7% and femoral neck BMD by 2.8% compared to placebo in postmenopausal women with osteoporosis. 2

• In postmenopausal women, 96% experienced increased lumbar spine BMD from baseline, with 72% achieving at least 5% increase and 44% gaining 10% or more. 2

• In men with primary or hypogonadal osteoporosis, teriparatide increased lumbar spine BMD by 5.9% compared to 0.5% with placebo (p<0.001) after median 10 months of treatment. 2

• For glucocorticoid-induced osteoporosis, teriparatide increased lumbar spine BMD by 7.2%, total hip by 3.6%, and femoral neck by 3.7% (p<0.001 all sites) over 18 months. 2

Bone Quality and Histology

• Bone histology evaluations in 35 postmenopausal women treated for 12-24 months showed normal mineralization with no evidence of cellular toxicity. 2

• New bone formed with teriparatide was of normal quality, evidenced by absence of woven bone and marrow fibrosis. 2

Efficacy in Special Populations

• Teriparatide effectiveness is consistent regardless of age, baseline rate of bone turnover, and baseline BMD in men with osteoporosis. 2

• In glucocorticoid-induced osteoporosis, treatment effects were consistent across subgroups defined by gender, age, geographic region, body mass index, underlying disease, prevalent vertebral fracture, baseline glucocorticoid dose, and prior bisphosphonate use. 2

Comparative Effectiveness

• In type 2 diabetic patients with osteoporosis, teriparatide increased BMD of the whole femur (from 0.73 to 0.74 g/cm², p=0.011) and femoral neck (from 0.59 to 0.60 g/cm², p=0.011), whereas bisphosphonates and no medication showed no change. 5

• Combined teriparatide and low-intensity aerobic exercise improved both trabecular and cortical bone strength more effectively than either intervention alone in type 2 diabetes model rats. 6

Safety Considerations

• Teriparatide caused osteosarcoma in rats during drug testing, but no increased risk has been observed in adult humans treated with teriparatide. 2

• Patients should be monitored for symptoms of hypercalcemia (nausea, vomiting, constipation, lethargy, muscle weakness). 2

• Orthostatic hypotension may occur; patients should be prepared to sit or lie down during or after administration if they feel lightheaded or have palpitations. 2

• Teriparatide may have acute, subclinical adverse impact on stimulated glucose levels in osteoporotic women, with glucose levels at 90 and 120 minutes during OGTT increasing significantly after acute administration, though this effect tends to subside with chronic use. 7

Practical Implementation

For GLP-1 Receptor Agonists

• Treatment regimens should include GLP-1 receptor agonists for adults with type 2 diabetes and established/high risk of atherosclerotic cardiovascular disease, heart failure, and/or chronic kidney disease. 1

• Prior authorization typically requires documentation of: current HbA1c levels, previous medication trials and failures (particularly metformin), specific clinical indications, and presence of cardiovascular disease or risk factors. 3

• Most insurance plans follow step therapy requiring documented failure with metformin before approving GLP-1 receptor agonists. 3

For Teriparatide

• Administer 20 mcg subcutaneously once daily in the thigh or abdomen (not into vein or muscle). 2

• Store under refrigeration at 2°C to 8°C (36°F to 46°F) at all times; do not freeze. 2

• Each delivery device contains enough medicine for 28 days and should be discarded after this period even if solution remains. 2

• All patients should receive 1000 mg calcium and at least 400-800 IU vitamin D supplementation daily. 2