Side effects of Tesamorelin: joint pain, water retention, and changes in blood sugar levels

The most commonly reported side effects of tesamorelin include injection site reactions, joint pain, muscle discomfort, mild fluid retention, swelling, and occasional alterations in blood sugar regulation, although clinical trials have generally shown tesamorelin to be relatively well tolerated by most participants [1–9]. Tesamorelin works by increasing activity of the naturally occurring growth hormone (GH) and insulin-like growth factor-1 (IGF-1), and it is believed that some of the adverse events are related to increased stimulation of these hormonal pathways.

Joint pain is one of the more commonly reported adverse events in tesamorelin studies. Some participants experienced arthralgia, or joint pain, along with stiffness, muscle aches, or discomfort in their arms and legs [1,2,8]. These symptoms are similar to effects sometimes seen with therapies that increase GH and IGF-1 signaling. In most studies, joint-related adverse events were described as mild to moderate, rather than severe.

Water retention and mild oedema have also been observed during tesamorelin treatment. Peripheral oedema, which is the accumulation of fluid causing swelling in areas such as the hands, feet, or ankles, developed in some individuals [1,3,8]. Growth hormone signalling may influence the balance of sodium and water within tissues, which could contribute to temporary fluid retention in some people. Clinical trials generally considered these effects to be manageable and rarely required discontinuation of treatment.

Reactions at the injection site are among the most frequently reported side effects of tesamorelin. Redness, itching, irritation, mild pain, bruising, or swelling around the administration site have often been described in clinical trials [1–4]. As tesamorelin is administered daily as a subcutaneous injection, meaning an injection into the fatty tissue under the skin, mild local skin reactions may occur during treatment.

Blood glucose levels and glucose metabolism were closely monitored in studies of tesamorelin as the GH and IGF-1 pathways can affect insulin sensitivity and glucose regulation. Most large clinical trials have shown that tesamorelin did not cause a significant worsening of fasting glucose or HbA1c in the majority of participants [2–7]. HbA1c is a blood test that reflects average blood sugar levels over several months. For example, Stanley et al. (2019) found no significant differences in fasting glucose or HbA1c between the tesamorelin and placebo groups during a 12-month study of HIV-associated non-alcoholic fatty liver disease (NAFLD) [5]. Similarly, the pooled Phase III trials by Falutz et al. (2010) demonstrated stable blood glucose control despite significant reductions in visceral fat and increases in IGF-1 levels [2].

However, some studies have observed slight increases in blood sugar markers in some participants. Rahman et al. (2023) reported a mild increase in HbA1c in some responder and non-responder groups during further analyses of phase III trials, although the changes were generally small [8]. Baker et al. (2012) also observed a slight increase in fasting insulin in older adults receiving tesamorelin during cognitive function studies, although values remained within normal physiological ranges [9]. As tesamorelin can increase IGF-1 levels and affect glucose metabolism, regular monitoring of blood sugar and IGF-1 levels is often recommended during treatment.

Other less commonly reported adverse events observed in trials of tesamorelin include:

• muscle pain (myalgia)
• tingling or numbness (paresthesia)
• nausea
• Headache
• mild hypersensitivity reactions or allergic reactions
• elevated IGF-1 levels
• Bruising or irritation at the injection site

Importantly, long-term clinical studies have generally shown tesamorelin to be relatively safe and well-tolerated when used under appropriate medical supervision [1–8]. Falutz et al. (2008) demonstrated sustained reductions in visceral fat for 52 weeks without significant worsening of glycaemic control or severe systemic toxicity [3]. A meta-analysis published by Badran et al. (2026) also found tesamorelin to improve body composition and reduce liver fat without causing serious adverse events or major glycaemic disturbances, though joint pain, muscle aches, tingling, and injection site reactions occurred more frequently than in the placebo group [10].

As tesamorelin increases GH and IGF-1 activity, caution is generally advised in individuals with active malignancy, uncontrolled diabetes, severe endocrine disorders, or significant metabolic instability. Close monitoring by a qualified healthcare professional is important during treatment.

Disclaimer

The content is for educational and informational purposes only and should not be interpreted as medical advice, diagnosis or therapeutic recommendation. Tesamorelin is a prescription medication that can cause adverse side effects and requires medical supervision, laboratory monitoring, and individual assessment by a qualified healthcare professional.