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Expert Witness Insights by Area of Expertise
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Pharmaceutical, Epidemiology, Pharmacology, Cardiology, Biostatistics
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Saxagliptin expert testimony became central to the Onglyza MDL’s dispute over general causation and heart failure. This article explains why the plaintiffs’ expert was excluded, including concerns involving contrary human studies, animal research, Bradford Hill analysis, expert qualifications, and reliable application of scientific methodology under Rule 702.
Expert testimony became the decisive issue in multidistrict litigation alleging that saxagliptin, a medication used to treat type 2 diabetes, could cause heart failure.
In In re Onglyza (Saxagliptin) and Kombiglyze (Saxagliptin and Metformin) Products Liability Litigation, the U.S. Court of Appeals for the Sixth Circuit affirmed the exclusion of the plaintiffs' sole general-causation expert and the resulting summary judgment for the defendants. The court identified significant concerns with the reliability of the proposed causation analysis.
The February 13, 2024 decision shows how courts may examine expert qualifications, contrary scientific evidence, and the reliable application of scientific methodology.
This guide explains the scientific evidence behind the dispute, why the expert was excluded, how Rule 702 applied, and what the decision means for pharmaceutical causation testimony.
The litigation centered in part on the SAVOR cardiovascular outcomes trial, a randomized controlled trial involving 16,492 patients with type 2 diabetes and cardiovascular disease or cardiovascular risk factors.
The trial found no statistically significant difference between saxagliptin and placebo for its primary cardiovascular endpoint. Hospitalization for heart failure, however, occurred in 3.5% of patients assigned saxagliptin and 2.8% assigned placebo, with a reported hazard ratio of 1.27.
The authors cautioned that the heart-failure finding was unexpected, should be considered in light of multiple statistical comparisons and the possibility of a false-positive result, and required further investigation and confirmation.
The saxagliptin label was later updated to include a heart-failure warning. The April 2016 FDA-approved prescribing information added a heart-failure warning, and the December 2025 Onglyza prescribing information continues to direct clinicians to consider the risks and benefits of saxagliptin in patients with known risk factors for heart failure.
An FDA warning, however, does not by itself establish that an expert's general-causation opinion satisfies Rule 702.
In February 2018, the U.S. Judicial Panel on Multidistrict Litigation transferred the federal actions to the Eastern District of Kentucky for coordinated or consolidated pretrial proceedings. At the time, 41 actions were pending in 23 federal districts, with another 43 potential tag-along actions reported in 26 districts.
The district court first directed discovery to general causation, meaning whether saxagliptin was capable of causing the injuries alleged by the plaintiffs.
The plaintiffs designated Dr. Parag Goyal, a cardiology professor at Weill Cornell Medicine, as their sole general-causation expert. He opined that saxagliptin was more likely than not capable of causing heart failure.
After a Daubert hearing, the district court excluded Dr. Goyal's testimony on January 5, 2022. On August 2, 2022, the court granted summary judgment for the defendants and denied the plaintiffs' request for an additional 90 days to identify another general-causation expert. The Sixth Circuit affirmed in 2024.
Causation Analysis
Drug Regulation
Evidence Analysis
Litigation Support
Expert testimony became the decisive issue in multidistrict litigation alleging that saxagliptin, a medication used to treat type 2 diabetes, could cause heart failure.
In In re Onglyza (Saxagliptin) and Kombiglyze (Saxagliptin and Metformin) Products Liability Litigation, the U.S. Court of Appeals for the Sixth Circuit affirmed the exclusion of the plaintiffs' sole general-causation expert and the resulting summary judgment for the defendants. The court identified significant concerns with the reliability of the proposed causation analysis.
The February 13, 2024 decision shows how courts may examine expert qualifications, contrary scientific evidence, and the reliable application of scientific methodology.
This guide explains the scientific evidence behind the dispute, why the expert was excluded, how Rule 702 applied, and what the decision means for pharmaceutical causation testimony.
The litigation centered in part on the SAVOR cardiovascular outcomes trial, a randomized controlled trial involving 16,492 patients with type 2 diabetes and cardiovascular disease or cardiovascular risk factors.
The trial found no statistically significant difference between saxagliptin and placebo for its primary cardiovascular endpoint. Hospitalization for heart failure, however, occurred in 3.5% of patients assigned saxagliptin and 2.8% assigned placebo, with a reported hazard ratio of 1.27.
The authors cautioned that the heart-failure finding was unexpected, should be considered in light of multiple statistical comparisons and the possibility of a false-positive result, and required further investigation and confirmation.
The saxagliptin label was later updated to include a heart-failure warning. The April 2016 FDA-approved prescribing information added a heart-failure warning, and the December 2025 Onglyza prescribing information continues to direct clinicians to consider the risks and benefits of saxagliptin in patients with known risk factors for heart failure.
An FDA warning, however, does not by itself establish that an expert's general-causation opinion satisfies Rule 702.
In February 2018, the U.S. Judicial Panel on Multidistrict Litigation transferred the federal actions to the Eastern District of Kentucky for coordinated or consolidated pretrial proceedings. At the time, 41 actions were pending in 23 federal districts, with another 43 potential tag-along actions reported in 26 districts.
The district court first directed discovery to general causation, meaning whether saxagliptin was capable of causing the injuries alleged by the plaintiffs.
The plaintiffs designated Dr. Parag Goyal, a cardiology professor at Weill Cornell Medicine, as their sole general-causation expert. He opined that saxagliptin was more likely than not capable of causing heart failure.
After a Daubert hearing, the district court excluded Dr. Goyal's testimony on January 5, 2022. On August 2, 2022, the court granted summary judgment for the defendants and denied the plaintiffs' request for an additional 90 days to identify another general-causation expert. The Sixth Circuit affirmed in 2024.
The Sixth Circuit identified several reliability problems with Dr. Goyal's causation analysis, including his treatment of contrary human studies, his use of animal research, and his application of the Bradford Hill considerations.
The court concluded that Dr. Goyal's heavy reliance on SAVOR, without adequately addressing other human evidence, undermined the reliability of his causation opinion.
The Sixth Circuit noted that four post-SAVOR observational studies involving approximately 175,000 saxagliptin users had not found an association with heart failure. Dr. Goyal acknowledged that the studies were reasonably designed but did not adequately explain why their results should be discounted.
The Sixth Circuit rejected the plaintiffs' argument that the district court had imposed a per se rule against relying on an unreplicated study. Instead, the court concluded that Dr. Goyal applied his methodology inconsistently because he acknowledged the importance of replication but, without adequate explanation, disregarded the other human studies. The court also faulted him for failing to adequately explain how he inferred a causal relationship from SAVOR, which reported an association but did not itself reach a causation conclusion.
The court also identified concerns with Dr. Goyal's interpretation of animal studies.
Dr. Goyal acknowledged that he was not qualified to determine whether the animals in the studies he cited actually had heart failure or whether saxagliptin was capable of causing heart failure in animals. The Sixth Circuit held that the district court did not err in finding his use of the animal studies unreliable.
The court also noted that Dr. Goyal had disregarded other peer-reviewed animal studies that the court described as dispelling a causal link between saxagliptin and heart failure. The decision illustrates why an expert's qualifications must support the specialized scientific interpretations used to form an opinion.
The Bradford Hill considerations provide a scientific framework for evaluating whether an observed association supports a causal inference.
The Sixth Circuit recognized Bradford Hill as a reliable methodology but held that Dr. Goyal did not apply it reliably. The court identified what it characterized as cherry-picking in his analogy analysis because he relied on thiazolidinediones rather than other DPP-4 inhibitors. It also identified unexplained inconsistencies in his treatment of the specificity and biological-gradient factors.
The decision therefore highlights the distinction between using a reliable methodology and reliably applying that methodology to the evidence, a distinction expressly reflected in current Rule 702.
Under Federal Rule of Evidence 702, the proponent of expert testimony must demonstrate to the court, by a more-likely-than-not standard, that Rule 702's admissibility requirements are satisfied.
The witness must first be qualified as an expert by knowledge, skill, experience, training, or education.
Expert testimony must also:
Because the district court ruled before the December 1, 2023 amendment to Rule 702 took effect, the Sixth Circuit applied the earlier version of the rule. The court nevertheless stated that the district court's reasoning was consistent with the amended rule and that the result would have been the same.
The decision reinforces that using a recognized methodology is not enough by itself. Courts may also examine how the expert applied that methodology to the evidence.
After Dr. Goyal's testimony was excluded, the plaintiffs argued that other evidence could still allow a jury to determine whether saxagliptin was capable of causing heart failure.
The Sixth Circuit upheld the district court's conclusion that the medically complex general-causation question presented in the MDL required expert testimony because it involved matters outside ordinary lay knowledge.
The Sixth Circuit also concluded that the district court did not err in determining that the jurisdictions implicated by the plaintiffs' claims required expert testimony to establish general causation in a complex medical case of this kind.
That conclusion should not be read as establishing that expert testimony is required for every type of injury or causation dispute. Whether expert testimony is necessary depends on the governing substantive law and the nature and complexity of the causation issue.
The Onglyza decision offers several practical lessons for pharmaceutical causation testimony.
A causation expert should address important contrary scientific evidence and explain how competing findings affect the analysis. Selectively relying on supportive evidence while failing to adequately address significant contrary studies may create a Rule 702 reliability problem.
Counsel should also confirm that the expert's qualifications match the scientific issues underlying the opinion. Depending on the dispute, relevant disciplines may include cardiology, pharmacology, toxicology, epidemiology, and biostatistics.
When an expert uses Bradford Hill or another recognized methodology, the analysis should clearly explain how the evidence supports the opinion and apply the methodology consistently to both supporting and contrary evidence.
FDA warnings may be relevant to a pharmaceutical causation dispute, but they do not by themselves establish that a causation opinion satisfies Rule 702.
The case also shows the procedural risk of relying on one expert for a threshold issue. After the plaintiffs' sole general-causation expert was excluded, the district court declined to reopen the expert schedule and grant an additional 90 days for a replacement expert. The Sixth Circuit found no abuse of discretion.
Did the Sixth Circuit rule that saxagliptin cannot cause heart failure?
No. The court decided whether the plaintiffs' proposed general-causation testimony was admissible and whether their claims could continue without admissible expert testimony on general causation. It did not hold that saxagliptin can never cause heart failure.
Did the SAVOR trial establish that saxagliptin causes heart failure?
No. SAVOR found a statistically significant increase in hospitalization for heart failure among patients assigned saxagliptin, but the authors cautioned that the finding was unexpected, should be considered in light of multiple statistical comparisons and the possibility of a false-positive result, and required further investigation and confirmation.
Why was the FDA heart-failure warning not enough to establish general causation?
FDA warnings address drug safety and risk communication. In litigation, the parties must separately satisfy the applicable substantive law and evidentiary requirements, including the need for admissible expert testimony when the causation issue requires specialized scientific or medical knowledge.
Does Rule 702 require courts to evaluate how an expert applies a methodology?
Yes. Current Rule 702 requires both reliable principles and methods and a reliable application of those principles and methods to the facts of the case.
Can a party replace an expert after the expert is excluded?
Not automatically. Whether a replacement expert may be identified depends on the applicable procedural rules, the court's scheduling order, and the circumstances of the case. In the Onglyza MDL, the district court denied the plaintiffs' request for an additional 90 days to identify another general-causation expert, and the Sixth Circuit affirmed that ruling.
The Sixth Circuit identified several reliability problems with Dr. Goyal's causation analysis, including his treatment of contrary human studies, his use of animal research, and his application of the Bradford Hill considerations.
The court concluded that Dr. Goyal's heavy reliance on SAVOR, without adequately addressing other human evidence, undermined the reliability of his causation opinion.
The Sixth Circuit noted that four post-SAVOR observational studies involving approximately 175,000 saxagliptin users had not found an association with heart failure. Dr. Goyal acknowledged that the studies were reasonably designed but did not adequately explain why their results should be discounted.
The Sixth Circuit rejected the plaintiffs' argument that the district court had imposed a per se rule against relying on an unreplicated study. Instead, the court concluded that Dr. Goyal applied his methodology inconsistently because he acknowledged the importance of replication but, without adequate explanation, disregarded the other human studies. The court also faulted him for failing to adequately explain how he inferred a causal relationship from SAVOR, which reported an association but did not itself reach a causation conclusion.
The court also identified concerns with Dr. Goyal's interpretation of animal studies.
Dr. Goyal acknowledged that he was not qualified to determine whether the animals in the studies he cited actually had heart failure or whether saxagliptin was capable of causing heart failure in animals. The Sixth Circuit held that the district court did not err in finding his use of the animal studies unreliable.
The court also noted that Dr. Goyal had disregarded other peer-reviewed animal studies that the court described as dispelling a causal link between saxagliptin and heart failure. The decision illustrates why an expert's qualifications must support the specialized scientific interpretations used to form an opinion.
The Bradford Hill considerations provide a scientific framework for evaluating whether an observed association supports a causal inference.
The Sixth Circuit recognized Bradford Hill as a reliable methodology but held that Dr. Goyal did not apply it reliably. The court identified what it characterized as cherry-picking in his analogy analysis because he relied on thiazolidinediones rather than other DPP-4 inhibitors. It also identified unexplained inconsistencies in his treatment of the specificity and biological-gradient factors.
The decision therefore highlights the distinction between using a reliable methodology and reliably applying that methodology to the evidence, a distinction expressly reflected in current Rule 702.
Under Federal Rule of Evidence 702, the proponent of expert testimony must demonstrate to the court, by a more-likely-than-not standard, that Rule 702's admissibility requirements are satisfied.
The witness must first be qualified as an expert by knowledge, skill, experience, training, or education.
Expert testimony must also:
Because the district court ruled before the December 1, 2023 amendment to Rule 702 took effect, the Sixth Circuit applied the earlier version of the rule. The court nevertheless stated that the district court's reasoning was consistent with the amended rule and that the result would have been the same.
The decision reinforces that using a recognized methodology is not enough by itself. Courts may also examine how the expert applied that methodology to the evidence.
After Dr. Goyal's testimony was excluded, the plaintiffs argued that other evidence could still allow a jury to determine whether saxagliptin was capable of causing heart failure.
The Sixth Circuit upheld the district court's conclusion that the medically complex general-causation question presented in the MDL required expert testimony because it involved matters outside ordinary lay knowledge.
The Sixth Circuit also concluded that the district court did not err in determining that the jurisdictions implicated by the plaintiffs' claims required expert testimony to establish general causation in a complex medical case of this kind.
That conclusion should not be read as establishing that expert testimony is required for every type of injury or causation dispute. Whether expert testimony is necessary depends on the governing substantive law and the nature and complexity of the causation issue.
The Onglyza decision offers several practical lessons for pharmaceutical causation testimony.
A causation expert should address important contrary scientific evidence and explain how competing findings affect the analysis. Selectively relying on supportive evidence while failing to adequately address significant contrary studies may create a Rule 702 reliability problem.
Counsel should also confirm that the expert's qualifications match the scientific issues underlying the opinion. Depending on the dispute, relevant disciplines may include cardiology, pharmacology, toxicology, epidemiology, and biostatistics.
When an expert uses Bradford Hill or another recognized methodology, the analysis should clearly explain how the evidence supports the opinion and apply the methodology consistently to both supporting and contrary evidence.
FDA warnings may be relevant to a pharmaceutical causation dispute, but they do not by themselves establish that a causation opinion satisfies Rule 702.
The case also shows the procedural risk of relying on one expert for a threshold issue. After the plaintiffs' sole general-causation expert was excluded, the district court declined to reopen the expert schedule and grant an additional 90 days for a replacement expert. The Sixth Circuit found no abuse of discretion.
Did the Sixth Circuit rule that saxagliptin cannot cause heart failure?
No. The court decided whether the plaintiffs' proposed general-causation testimony was admissible and whether their claims could continue without admissible expert testimony on general causation. It did not hold that saxagliptin can never cause heart failure.
Did the SAVOR trial establish that saxagliptin causes heart failure?
No. SAVOR found a statistically significant increase in hospitalization for heart failure among patients assigned saxagliptin, but the authors cautioned that the finding was unexpected, should be considered in light of multiple statistical comparisons and the possibility of a false-positive result, and required further investigation and confirmation.
Why was the FDA heart-failure warning not enough to establish general causation?
FDA warnings address drug safety and risk communication. In litigation, the parties must separately satisfy the applicable substantive law and evidentiary requirements, including the need for admissible expert testimony when the causation issue requires specialized scientific or medical knowledge.
Does Rule 702 require courts to evaluate how an expert applies a methodology?
Yes. Current Rule 702 requires both reliable principles and methods and a reliable application of those principles and methods to the facts of the case.
Can a party replace an expert after the expert is excluded?
Not automatically. Whether a replacement expert may be identified depends on the applicable procedural rules, the court's scheduling order, and the circumstances of the case. In the Onglyza MDL, the district court denied the plaintiffs' request for an additional 90 days to identify another general-causation expert, and the Sixth Circuit affirmed that ruling.
Causation Analysis
Drug Regulation
Evidence Analysis
Litigation Support
Expert Witness Insights by Area of Expertise
Expert Witness Insights by Area of Expertise