Exploring Jupiter—An important clinical trial

In a landmark clinical trial called Jupiter, scientists sought to assess the impact of 20 mg/day of rosuvastatin vs. placebo in more than 17,000 HIV-negative participants whom they described as “apparently healthy.” In other words, these participants were seemingly at low risk for a heart attack or other major cardiovascular event.

Researchers involved with the Jupiter study have reanalyzed the data to assess the impact of rosuvastatin on the development of diabetes.

Study details

Enrolled participants did not have any history of diabetes. However, upon entering the study, many participants had what researchers called “major risk factors for diabetes,” such as the following:

  • metabolic syndrome – this term refers to a cluster of risk factors such as excess waist size, elevated levels of fatty substances in the blood (triglycerides), less-than-ideal levels of good cholesterol (HDL-C) in the blood, higher-than-normal blood pressure, elevated levels of fasting blood sugar (more than 5.5 mmol/L but less than 6.99 mmol/L)
  • high fasting blood sugar
  • abnormal average blood sugar in red blood cells (this is called hemoglobin A one C, written as HbA1C)
  • being overweight or obese

Researchers analysed data collected from 17,603 participants. Participants were monitored for up to five years.


In analysing the data, here are some of the findings at the start of the study:

  • 6,095 participants had no major diabetes risk factors
  • 11,508 participants had one or more major diabetes risk factors
  • participants with no major diabetes risk factors were more likely to smoke tobacco

According to researchers, participants who had one or more major diabetes risk factors at the start of the study were “more likely to be female” and have higher-than-normal levels of the following:

  • blood pressure
  • HbA1C
  • fasting blood sugar
  • triglycerides


Overall, participants who had one or more major diabetes risk factors when they entered the study had about an 11-fold increased risk for developing this complication while in the study.

Who was at risk?

When researchers analysed which of the participants who developed diabetes were taking rosuvastatin or placebo, they found that, overall, cases of diabetes were somewhat more common among participants who received rosuvastatin (270 cases) than among those who received placebo (216 cases).

This amounted to a 25% overall increased risk for developing diabetes among rosuvastatin users. However, this is not the final word on this risk, as researchers made the following statement:

“Almost all the excess risk of diabetes associated with rosuvastatin occurred in participants with [evidence of abnormal blood sugar levels when they entered the study].”

Another way to look at the study’s findings is as follows:

  • About 2% of people with major diabetes risk factors who took rosuvastatin developed diabetes.

Other side effects

The rate of other side effects seen in Jupiter was similar (about 15%) whether participants were taking rosuvastatin or placebo. This points to the relative safety and tolerability of statins.

Historically, statins have been found to sometimes cause the following side effects:

  • muscular issues – stiffness, weakness or pain (usually not severe)
  • rhabdomyolysis – the breakdown of muscle, causing the release of the protein myoglobin into the blood; myoglobin is broken down into substances that can injure the kidneys (extremely rare side effect)

In Jupiter, the proportions of participants who reported muscle stiffness, weakness or pain were very similar in participants who received either placebo or rosuvastatin (15% and 16%, respectively). This difference was not statistically significant. It shows that, on average, low-dose rosuvastatin is generally well tolerated and has similar side effects to a placebo.

One case of rhabdomyolysis occurred (representing 0.1% of participants) in a person taking rosuvastatin and no cases occurred in participants taking placebo.

Rosuvastatin—preventing serious problems

Among participants who had at least one major diabetes risk factor when they entered the study, rosuvastatin reduced their risk of the following by 39% when compared to placebo:

  • heart attack
  • sudden and temporary chest pain or discomfort while resting (unstable angina); such pain was linked to circulatory problems
  • having major cardiac surgery such as implanting a stent or transplanting blood vessels to help improve the heart’s ability to move blood to the rest of the body (coronary bypass)
  • death from cardiovascular complications

This difference in risk reduction caused by rosuvastatin compared to placebo was statistically significant; that is, not likely due to chance alone.

Points of interest

  1. Jupiter was a very large placebo-controlled study with monitoring lasting for up to five years (though participants were in the double-blind phase for about two years). Its findings are therefore powerful.
  2. At the start of the study, all participants had elevated levels of inflammation, as measured with high-sensitivity C-reactive protein (hsCRP) testing of the blood.
  3. The risk of developing diabetes among participants taking rosuvastatin was limited to people who were already at high risk for diabetes. Such people had lab tests suggestive of abnormal blood sugar or elevated HbA1C, or obesity, or a collection of risk factors called the metabolic syndrome.
  4. The study researchers noted that the cardiovascular and survival benefits of rosuvastatin “exceeded the diabetes hazard in the trial population as a whole as well as in participants at increased risk of developing diabetes.”
  5. The cardiovascular benefits of rosuvastatin were accompanied by an earlier onset of diabetes (by about six weeks). The researchers noted that “whether this finding has clinical relevance is uncertain because [in the community] most patients with diabetes are treated with statin therapy.” There was no difference in the risk of developing diabetes by age. That is, older and younger participants had similar risks when given rosuvastatin.

Just one piece of the puzzle

The study researchers noted that statins are meant to be used as part of a plan that has at least the following elements:

  • healthier dietary habits
  • increased levels of exercise
  • quitting smoking

Advice from researchers

In an editorial to accompany this analysis of Jupiter, cardiovascular researchers encouraged doctors who treat patients who have major diabetes risk factors to do the following:

  • inform patients about the potential risk of statins
  • monitor their blood sugar regularly
  • advise them to lose weight
  • encourage them to engage in regular exercise

A super study and weight

A different study has performed a re-analysis of 20 randomized clinical trials of statins and confirms that these drugs can increase the risk for developing diabetes. Researchers with this massive re-analysis suggest that the increased risk for developing diabetes is linked to increased weight. This supports the previously mentioned advice from Jupiter researchers that people with major risk factors for diabetes need to lose weight.

For the future

As mentioned earlier in this issue of TreatmentUpdate, studies with statins are likely to be undertaken with HIV-positive people in order to assess the ability of such medicines to reduce the risk for cardiovascular disease and inflammation. Although the Jupiter trial enrolled HIV-negative people, one study with HIV-positive people has released preliminary results. That study, called Saturn, is discussed in the next article.

—Sean R. Hosein


  1. Ganesan A, Crum-Cianflone N, Higgins J, et al. High-dose atorvastatin decreases cellular markers of immune activation without affecting HIV-1 RNA levels: results of a double-blind randomized placebo controlled clinical trial. Journal of Infectious Diseases. 2011 Mar 15;203(6):756-64.
  2. Ridker PM, Pradhan A, MacFadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012 Aug 11;380(9841):565-71.
  3. Swerdlow DI, Preiss D, Kuchenbaecker KB, et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet. 2014; in press.
  4. Frayling TM. Statins and type 2 diabetes: genetic studies on target. Lancet. 2014; in press.
  5. Watts GF, Ooi EM. Balancing the cardiometabolic benefits and risks of statins. Lancet. 2012 Aug 11;380(9841):541-3.
  6. Zhang H, Plutzky J, Skentzos S, et al. Discontinuation of statins in routine care settings: a cohort study. Annals of Internal Medicine. 2013 Apr 2;158(7):526-34.